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Acute Kidney Injury

Lisa Crowley and Marlies Ostermann  -  Review Date June 2016

Acute kidney injury (AKI) is a common and important clinical problem which affects 13-18% of patients admitted to hospital. It is associated with increased morbidity and mortality, a longer stay in hospital and high health care costs. (Chertow, 2005; Fischer, 2005; Lafrance, 2010). Survivors of AKI have an increased risk of short and long-term complications, including chronic kidney disease (Coca, 2009; Lo, 2009, Wald, 2009). The costs of AKI to the National Health Service are estimated to be between £434 -620 million per year which is more than the costs associated with the most common cancers (NICE AKI Guideline, 2013).


The RIFLE criteria for AKI (Bellomo, 2004)

In 2004, an international expert group of renal and intensive care clinicians proposed to change the term “acute renal failure” to “acute kidney injury” to better describe the spectrum of renal disease. In addition, they proposed a universal definition and staging system for AKI, termed RIFLE which incorporates 3 stages of severity (Risk, Injury and Failure) and 2 outcome criteria (Loss of renal function, End stage renal failure).


­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­ Figure: Rifle Criteria for Diagnosis of AKI

The purpose was to increase awareness about AKI and to improve the recognition and management at an earlier stage.

Acute Kidney Injury Network (AKIN) classification (Mehta, 2007)

In response to a large single center study which showed that even relatively small rises in serum creatinine of 0.3mg/dL or more (≥26.4μmol/L) were independently associated with an increased risk of dying, the RIFLE classification was revised by the AKI network.

The AKI Network proposed the following definition for AKI:­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­ ­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­

“An abrupt (within 48 hours) reduction in kidney function currently defined as an absolute increase in serum creatinine of ≥0.3mg/dl (≥26.4μmol/L), a percentage increase in serum creatinine of ≥50% (1.5 fold from baseline), or a reduction in urine output (documented oliguria of less than 0.5ml/kg per hour for ≥6 hours).”

Once the criteria for AKI are fulfilled, three stages can be distinguished:

Stage 1

Increase in serum creatinine ≥26.2 μmol/L or increase to ≥150–199% (1.5- to 1.9 fold) from baseline; OR urine output <0.5 mL/kg/h for ≥6 h

Stage 2

Increase in serum creatinine to 200–299% (>2–2.9 fold) from baseline; OR UO <0.5 mL/kg/h for ≥12 h

Stage 3

Increase in serum creatinine to ≥300% (≥3-fold) from baseline OR serum creatinine ≥354 μmol/L with an acute rise of at ­ least 44 μmol/L OR initiation of RRT (independent of serum creatinine) OR anuria >12h; OR UO <0.3 mL/kg/h for ≥24 h

KDIGO classification (KDIGO, 2012)

KDIGO classification

In 2012, the Kidney Disease Improving Global Outcomes (KDIGO) Group published the KDIGO classification for AKI in an attempt to harmonise the RIFLE and AKIN criteria.

As per KDIGO, AKI is defined as any of the following:

  1. Increase in serum creatinine by ≥0.3mg/dl (≥26.4 μmol/l) within 48 hours; OR
  2. Increase in serum creatinine to ≥ 1.5 times baseline which is known or presumed to have occurred within prior 7 days; OR
  3. Urine volume <0.5ml/kg/hour for 6 hours

If these criteria are met, the cause of AKI should be ascertained and AKI should be staged as follows:

Stage 1: serum creatinine 1.5–1.9 times baseline or >0.3 mg/dl (>26.5 mcmol/l) increase (or UO <0.5 ml/kg/h for 6-12h)
Stage 2: serum creatinine 2.0–2.9 times baseline (or UO <0.5 ml/kg/h for >12h)
Stage 3: serum creatinine 3.0 times baseline (or increase in serum creatinine to >4.0 mg/dl (353.6 mcmol/l); or initiation of renal replacement therapy

Or in patients <18 years, decrease in eGFR to <35 ml/min per 1.73 m2 (or UO <0.3 ml/kg/h for >24h or anuria for >12 hours)­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­

National Institute for Clinical Excellence (NICE, 2013)

In 2013, the National Institute for Health and Care Excellence (NICE) published an AKI guideline which recommends to use either the RIFLE, AKIN or KDIGO criteria to define AKI.

The NICE recommendation states:

Detect AKI in line with the RIFLE, AKIN or KDIGO definitions, by using any of the following criteria:

  1. A­rise in serum creatinine of 26 μmol/l or greater within 48 hours;
  2. A­50% or greater rise in serum creatinine known or presumed to have occurred within the past 7 days
  3. A­fall in urine output to <0.5 ml/kg/hour for >6 hours in adults and >8 hours in children and young people
  4. A­25% or greater fall in eGFR in children and young people within the past 7 days.

Importantly, the term AKI describes a large spectrum of diseases, all characterised by a rise in serum creatinine and/or fall in urine output. AKI is not a diagnosis and does not refer to any aetiology. Once AKI is diagnosed, it is still important to identify the exact aetiology.

The difficulty of defining AKI has been debated by Ostermann (2010).


The incidence of AKI is determined by its definition and the population studied. Before the use of the RIFLE, AKIN or KDIGO criteria, estimates were based on arbitrary criteria and often variable and conflicting. AKI is common in sicker patients, in particular in critically ill patients in the Intensive Care Unit (ICU) where it affects 30-60% of patients. Outcome is worse in patients with more severe AKI, especially if renal replacement therapy (RRT) is needed.

There is clear evidence that AKI is not always recognised in time (NCEPOD, 2009). NHS Kidney Care estimates that a large proportion of cases of AKI are preventable. If prevented, lives would be saved, complications avoided and healthcare costs reduced.

Thomas et al developed an electronic early warning system to spot AKI at an earlier stage (and treat appropriately) – though a mortality (36%) similar to the literature, was seen (Thomas, 2011). In another hospital-based study by Selby et al, a similar electronic reporting system was described in a large general hospital (Selby, 2012) The results showed that there were 3202 AKI episodes in 2619 patients during the 9-month study period (5.4% of hospital admissions).

The exact incidence of AKI in the community is not clear (Thomas, 2013). It has been shown that a large proportion of AKI cases start with an illness in the community. Future studies using electronic alerting based on the recent AKI definitions may give a better picture of the epidemiology of AKI in the community.








Yadullah Syed and Marlies Ostermann  -  Review Date June 2016


Acute kidney Injury (AKI) is a term used to describe a variety of different diseases with heterogeneous aetiologies that lead to renal dysfunction with different prognostic outcomes. AKI has replaced the term 'acute renal failure' and describes a long list of conditions associated with acute renal dysfunction.­

History of AKI

William Heberden in 1802 described acute renal failure as 'Ischuria renalis', and in 1909 [1,2], William Osler’s textbook of medicine described it as acute Bright’s Disease. During the First World War, in 1917, Dr. F. Davies described it as 'war nephritis' in the Lancet [3]. The term acute renal failure was first used by Homer Smith in 1951 in his textbook The Kidney - Structure and Function in Health and Disease. The term 'AKI' was coined by the Acute Dialysis Quality Initiative (ADQI) in 2004 [4].


Acute kidney injury can be defined using RIFLE, AKIN ­or KDIGO criteria. The recent guideline by the UK's National Institute for Health and Care Excellence (NICE) recommends to define AKI in accordance with the AKIN, KDIGO and paediatric KDIGO classifications by any of the following: [5]

  • A rise in serum creatinine of ≥26 ­μmol/litre within 48­hours
  • A ≥ 50% rise in serum creatinine known or presumed to have occurred within the past 7­days
  • A fall in urine output to <0.5­ml/kg/hour for more than 6 ­hours in adults and more than 8 ­hours in children and young people
  • A ≥25% fall in estimated glomerular fitratlon rate (eGFR) in children and young people within the past 7­days

Note: The term ‘Adult’ refers to people who are aged ≥18 years, ‘Younger’ people to people 12-17 yrs of age, and 'Children' to subjects 11 years or younger (excluding neonates less than 1 month old). The reference creatinine is taken as the lowest creatinine level in the last 3 months. In the absence of previous blood results, admission creatinine is considered as the reference creatinine.

Pitfalls of various definition systems

  1. Creatinine is affected by non-renal variables , including muscle mass­, muscle dietary supplements, drugs that inhibit tubular creatinine secretion (eg H2 blockers) and laboratory techniques.
  2. Estimation of baseline renal function is difficult. In a patient with no previous serum creatinine result, the presentation creatinine acts as baseline. However, this approach is likely to lead to underdiagnosis of community acquired AKI.
  3. Small changes in serum creatinine may be blunted or exaggerated by changes in extracellular volume, and AKI may be missed or wrongly classified.
  4. Estimation of urine output is difficult without a urinary catheter in situ. Although this is not a major issue in ICU, it may be a problem in non-ICU settings.
  5. Serum creatinine rise can be delayed after definite renal injury. Patients may have acute tubular injury even if serum creatinine and urine output are still in the normal range.
  6. Pseudo AKI: Bilirubin, ascorbic acid, uric acid and certain drugs (eg cephalosporins, trimethoprim and cimetidine) may interfere with the creatinine assays. Therefore, it is important to be cautious and to interpret laboratory data in a clinical context.

Studies have used different classification systems to study the epidemiology of AKI. Not surprisingly, incidence and prevalence rates vary, depending on the classification system used, associated comorbid factors and subset of population studied. The same patient may be classified differently -­or may even not fulfil the AKI criteria - depending on the classification system. [6,7,8]

In developed countries, AKI is seen in 13-18% of all people admitted to hospital [5]. ­In critically ill patients AKI affects 20 - 60% of patients. [9,10,11,12,13,14,15] The high frequency of AKI amongst inpatients means that it has a major impact on patients and a­major economic impact. According to NHS Kidney Care, the cost of AKI to the NHS (excluding AKI in the community) is estimated to be between £434 million - £620 million per year. This­is more than the expenditure on breast cancer, lung and skin cancer combined [5]. Therefore any steps to prevent or treat AKI should have a positive outcome, at an individual patient level; and at the health care system level. AKI also carries increased short and long term morbidity and mortality, and a significant risk of ESRD.

Alemtuzumab (Campath®)

  • Humanised IgG1 monoclonal anti-CD52 antibody
  • Intravenous: injection 30mg vials

Alfacalcidol (1αhydroxycholecalciferol)

  • Alfacalcidol is an activated form of cholecalciferol (Vitamin D). Capsules: 0.25 micrograms, 0.5 micrograms, 1 microgram
  • Oral drops: 2 micrograms/ml (1 drop contains approximately 0.1 microgram). Injection: 2 micrograms/ml


Adam Rumjon and Iain Macdougall  -  Review Date October 2016 (Senior Editor Pete Topham)

Anaemia is a common and debilitating complication of chronic kidney disease that is seen in over 80% of patients with advanced renal impairment (Melnikova, 2006). Characteristically it is normochromic normocytic anaemia, with a low reticulocyte count. The haemoglobin level may fall to 6-8 g/dl, untreated, in ESRD patients.

To date, no studies have rigorously proven that anaemia in CKD causes an increase in mortality. However, a number of observational stuides have shown an association between degree of anaemia in CKD and an increased risk of death. Foley et al (1996) prospectively followed 432 ESRD patients and found that each 1 g/dl increase in haemoglobin was associated with a 14% decrease in­mortality risk.

Furthermore,­regarding morbidity, Collins (2001) found the risk of hospitalisation was lower in­HD patients with higher haemoglobin levels. The Canadian EPO study (and others that followed)­showed that correction of anaemia in CKD improves Quality of Life (CESG, 1990). Non-controlled studies have suggested­that correction of anaemia improves cognitive functions and sleep. Controlled studies have not shown that correction of anaemia corrects left ventricular hypertrophy (Foley, 2000).


Erythropoietin (EPO) deficiency is the primary underlying defect in the anaemia of CKD. Most EPO is made in the kidney, and the primary site of action is in the erythroid tissues of the bone marrow. The fact that EPO is detectable after bilateral nephrectomy is consistent with the experimental finding that 10% is produced by the liver.

Human erythropoietin is a sialglycoprotein composed of 165 amino acids. Human erythropoietin was purified in 1977, and the human erythropoietin gene was isolated by Lin in 1985. Recombinant human erythropoietin (rHuEPO) therapy was introduced­in 1986-7 (Winearls, 1986; Eschbach, 1987). Before then, dialysis patients were the frequent recipients of blood transfusions approximately every 2-3 weeks. This, however, subjected patients to­complications such as blood-borne viruses, iron overload and increased sensitivity to major histocompatibility antigens, lessening the chances for successful kidney transplantation.


Anaemia is defined as a state in which there is a reduced number of circulating red blood cells. Blood haemoglobin (Hb) concentration serves as the key indicator for anaemia because it can be measured directly, has an international standard, and is not influenced by differences in technology.

A previously established definition of anaemia constitutes a haemoglobin concentration lower than the established cut off defined by the World Health Organization (WHO, 2001), and different biological groups have different cut-off haemoglobin values below which anaemia is said to be present. This cutoff figure varies from 11 grams per decilitre (g/dl) for pregnant women and for children between 6 months and 5 years of age, to 12 g/dl for non-pregnant women, and to 13 g/dl for men. No downward adjustment for the elderly is made for age. Furthermore there is accumulating evidence that anaemia reflects illness and is associated with adverse outcomes in the elderly (Guralnik, 2004).

Target Haemoglobin and Iron Stores

The issue of haemoglobin targets has long been a contentious issue amongst clinicians (Macdougall, 2001)­and this is reflected in the disparity among the numerous clinical anaemia guidelines (in references). In addition to therapy with erythropoiesis-stimulating agents (ESAs), iron therapy is also a mainstay of treatment in the end-stage renal disease (ESRD) patient population; since iron is an essential ingredient for the synthesis of heme - and the subsequent production of red blood cells. Again, there is controversy regarding the appropriate target ranges for markers of iron status in ESRD patients.


The UK information concerning the prevalence of anaemia in patients with CKD comes from two studies (John, 2004; De Lusignan, 2005). The first of these population studies (John, 2004) examined the prevalence of CKD, defined as having a serum creatinine level of ≥130 μmol/l in women and ≥180 μmol/l in men, and found a rate of 5,554 per million population (pmp), with a median age of 82 years (range, 18 to 103 years), and a median calculated GFR of 28.0 ml/min/1.73m2 (range, 3.6 to 42.8 ml/min/1.73 m2).

Data for haemoglobin levels were available for 85.6% of patients. Mean haemoglobin concentration was 12.1±1.9 g/dl: 49.6% of men had haemoglobin levels less than 12 g/dl and 51.2% of women had levels less than 11 g/dl. Furthermore, in 27.5% of patients identified, the haemoglobin level was less than 11 g/dl, equivalent to nearly 90,000 of the population based on 2001 Census population figures.

The second, and larger, cross-sectional study abstracted data from 112,215 unselected patients with an age and sex profile representative of the general population (De Lusignan, 2005). Haemoglobin level was weakly correlated with eGFR (r=0.057, p <0.001). The population prevalence of stage 3–5 CKD in this study was estimated to be 4.9%. In those patients with stage 3–5 CKD, the prevalence of anaemia (defined as a haemoglobin level less than 12 g/dl in men and post-menopausal women, and less than 11 g/dl in pre-menopausal women) was 12.0%. Haemoglobin level was less than 11 g/dl in 3.8%, equivalent to over 108,000 of the population based on 2001 Census population figures.


First recorded in 1824. Derived from French medical term (1761), from Modern Latin, from Greek­anaimia ('lack of blood'), from anaimos ('bloodless'), from an- ('without')­+haima ('blood').


Anti-thymocyte globulin (ATG)

Thymoglobulin® - Rabbit anti-thymocyte globulin

Intravenous infusion; 25mg per vial.
Must be diluted before IV infusion in 0.9% sodium chloride or 5% glucose – usually into 50mls.
Once diluted, use immediately
It is recommended that Thymoglobuline is administered through a 0.22 μm in-line filter.

Atgam® - Equine anti-thymocyte globulin

Intravenous (IV) infusion; 50mg of equine gamma globulin per ml.
Must be diluted before IV infusion – final concentration should not exceed 4mg/ml.
Once diluted, use immediately.
Let the drug reach room temperature before IV infusion.
It is recommended that Thymoglobuline is administered through a 0.22 μm in-line filter


  • Anti-proliferative immunosuppressant
  • Preparations: Tablets: 25mg, 50mg
  • Azathioprine does NOT need to be prescribed by brand

Basiliximab (Simulect®)

  • A chimeric mouse-human monoclonal antibody to the α chain (CD25) of the IL-2 receptor of T cells
  • Intravenous injection: 10mg and 20mg vials

Calcium Salts

  • Phosphate-binding agent
  • Carbonate = Calcichew®, Adcal®, Cacit®
  • Acetate = Phosex®, Renacet®, PhosLo®

Chronic Kidney Disease

Stephanie Stringer, Sarah de Freitas and Paul Cockwell
Review Date October 2015 (Senior Editor Paul Cockwell)

Chronic kidney disease is described by KDIGO (Kidney Disease: Improving Global Outcomes) as ‘evidence of damaged renal parenchyma as demonstrated by active urinary sediment and/or structural abnormality (this must be present for stages 1 and 2 CKD) and/or evidence of decreased kidney function as demonstrated by a reduced glomerular filtration rate (GFR) and chronicity to distinguish it from acute kidney injury (AKI).’

Active urinary sediment refers to the presence of haematuria and/or proteinuria; ­the presence of haematuria or proteinuria may indicate glomerular pathology and the importance of proteinuria as a risk factor for CKD progression and CVD has become increasing recognised with time and will be described later in this topic. Structural abnormalities of the renal tract include kidney stones, cysts, renal scars. Individuals with structural kidney disease are at risk of progression and even in the absence of evidence of reduced GFR should be considered to have CKD. The current ­definition of CKD by KDIGO­ (Levey et al; 2011) comprises :

(i) presence of kidney damage for ≥ 3 months, with kidney damage defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies and/or

(ii) GFR <60 ml/min/1.73m2 for ≥ 3 months with or without kidney damage.

The definition of CKD has led to the development of a classification system for CKD. This has entered widespread use­and provides a system that is helpful both for clinical practice and for clinical and epidemiological research. The current classification system for CKD is shown in the table below.

*Chronicity is confirmed by the presence of abnormal kidney function by eGFR or proteinuria for >3 months

The majority of people with CKD are elderly and have sustained kidney damage as a consequence of vascular disease comprising one or more of hypertension, macrovascular disease and diabetes. For mild-moderate CKD the dominant causes are diabetes and hypertension. However as CKD progresses to severe (stage 4 and stage 5) CKD, there is a change of prevalence in causes of kidney disease with an increased proportion of younger patients with glomerulonephritis and genetic causes of CKD. This is because these diseases progress more rapidly and elderly patients have a major competing risk of early death as a consequence of CKD. A summary of the major causes of kidney disease in patients with advanced CKD is shown in table 1. For information on the causes of kidney disease in patients who are starting treatment for end-stage kidney disease then please see page 23 table 7 of the­ hyperlink.

It is unusual for people to get overt symptoms associated with CKD; and overt symptoms that are demonstrably associated with CKD are restricted to people with advanced CKD. The symptoms associated with advanced CKD are discussed later in this article.

Historically there has been a lack of recognition of CKD as a highly important chronic disease, both for the individual patient and in terms of the organisation of clinical services and the health economic implications of the disorder. In the past 10-years these shortfalls have systematically addressed. As a consequence of this there is now evidence developing from the UK and other countries that outcomes for people with CKD are Improving­ (UK Renal Registry report; 2010). There are also major health economic implications associated with­CKD, a high proportion of health care funding is used in managing patients with CKD.

What is the basis for classifying CKD?

One of the developments that facilitated the introduction of a classification system was increased accuracy in kidney function testing as a consequence of the adoption of the creatinine based Modification of Diet in Renal Disease (MDRD) study formula to produce an estimated glomerular filtration rate (eGFR) that provides a measurement of excretory kidney function of sufficient accuracy for use in clinical practice.

The MDRD equation was used by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) to frame the classification system that has become widely adopted in clinical practice, the current version of this is shown above. Guidelines were then developed (KDIGO 2002) that were based on observations that to improve the outcomes of patients on dialysis required a focus on the health of patients at risk of ESKD and that it may be possible to slow the rate of progression and reduce the complications of CKD by early identification and directed management.

The prevalence of and risk factors for ­CKD

The formalised reporting of eGFR led to better identification of the prevalence of kidney disease, with estimates of CKD in the developed world of up to 16% of the adult population. In the UK a recent report that utilised epidemiological data identified the prevalence of all CKD as 14% in men and 13% in women. The prevalence of CKD where there was a demonstrable reduction in excretory kidney function as defined by an eGFR of <60ml/min/1.73m2 (stage 3-5 CKD) was 6%.­Advanced CKD is uncommon; around 0.4% of the adult population has stage 4 CKD and 0.2% has stage 5­CKD.

End-stage kidney disease (ESKD)­ is rare, with new cases being very unusual. In 2009, the incidence of ­ESKD­ was 109 per million population (pmp) in UK adults, with 6730 new patients. So,

Key point: A renal unit that serves a million people, will start 2 patients with ­ESKD ­on dialysis per week.

Prevalence was 794 ­pmp in 2009, with 49,080­ ESKD ­patients. With an estimated UK population of 62, 262,000 in 2010, ­ESKD occurs in 1 in 1270 people,­ie ­about 0.1% of the population. So,

Key point: A ­GP ­practice­ with 8000 patients, will have around eight patient with ESKD (ie one per GP if there are 8 GPs, a typical number of patients/GP)

Risk factors

CKD is more common in women than in men, although men are more likely to progress to ESKD. The prevalence increases by age so that by the 8th decade of life over 30% of people have stage 3-5 CKD. However there is concern that there is over-classification of CKD in the elderly as a consequence of a component of the physiological decline in kidney function with age being assessed as pathological. Other risk factors for CKD include all cardiovascular disease groups and smoking. There are significant ethnic differences in CKD. People who are non-white are at increased risk of progressing to ESKD when they have CKD.

Pathophysiological considerations

Irrespective of the cause of kidney disease there are common processes that are characteristic of CKD and contribute to the progressive decline in kidney function that is seen in many patients. Loss of nephrons­is associated with glomerular­hypertension in the remaining glomeruli and progressive interstitial fibrosis, peritubular capillary loss and inflammation, including infiltration of mononuclear cells.

The pathophysiology of CKD has been reviewed by ­Yu (2003)Metcalfe (2007) ­and ­López-Novoa (2011).


Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD)

Paul Cockwell - Review Date July 2015 (Senior Editor Paul Cockwell)

Chronic Kidney Disease – Mineral Bone Disorder (CKD-MBD) is the term used to describe the pathophysiological changes that occur in the vascular and skeletal system in association with chronic kidney disease (CKD) (Moe et al). ­It has been classified by KDIGO in August 2009.­CKD-MBD has replaced the terms renal osteodystrophy and renal bone disease in routine clinical practice. The changes that occur in CKD-MBD include biochemical abnormalities, bone changes and extra-osseus (including vascular) calcification.

CKD- MBD can be diagnosed if a patient with CKD has evidence of one or more of:

1. ­Abnormalities of calcium, phosphate, PTH or vitamin D metabolism
2. ­Vascular and/or soft tissue calcification
3. ­Abnormalities in bone turnover, metabolism, volume, linear growth or strength

The development of CKD-MBD starts early in the course of CKD. Changes in serum levels of parathyroid hormone (PTH), 25-hydroxyvitamin D and 1,25 dihydroxyvitamin D are often present in patients with an estimated glomerular filtration rate (eGFR) of <60mL/min/1.73m2. Significant changes in serum calcium and phosphate levels can be seen with an eGFR <40mL/min. Whilst there are strong associations between CKD-MBD and adverse outcomes (both cardiovascular disease (CVD) morbidity and mortality and progressive CKD) (Eddington et al) there is little good quality evidence for interventions to address CKD-MBD in patients with less severe CKD (stages 3 and 4). Thus most clinicians focus treatment on patients with stage 5 CKD (eGFR <15mL/min/1.73m2).

To understand the pathophysiology of CKD-MBD requires an understanding of the central role of the kidney in calcium and phosphate homeostasis.


  • Calcineurin inhibitor
  • Brands available: Neoral®, Sandimmun®, Capimune®, Deximune®, Capsorin®
  • Neoral®, Capimune®, Deximune®, Capsorin® - available in capsules
  • Neoral® - oral liquid is available
  • IV Ciclosporin is available. Only IV preparation available is Sandimmun® brand
  • Prescribe by brand, do NOT switch between brands


  • Tablets: 30mg, 60mg, 90mg


  • Tablets - 50mg
  • Injection - slow IV bolus or in 100mls sodium chloride 0.9%

Darbepoetin Alfa (Aranesp®)

  • An Erythropoiesis-Stimulating Agent (ESA). Hyperglycosylated derivative of Epoetin
  • Darbepoetin (Aranesp®) prefilled syringe or sureclick pen: 10,15,20, 30, 40, 50, 60, 80, 100, 130, 150, 300, 500 micrograms

Epoetin Alfa (Eprex®)

  • An Erythropoiesis-Stimulating Agent (ESA)
  • Epoetin alfa injection = Eprex®, prefilled syringe 1000, 2000, 3000, 4000, 5000, 6000, 8000, 10000 units


Adam Kirk and James Tattersall - UNDER REVIEW  (Senior Editor Sunil Bhandari)

Haemodialysis is a method of removing excess fluid, salt and wastes from the blood, effectively replacing the excretion functions of failed kidneys.

Haemodialysis is used in hospitalised patients, particularly during critical illness causing acute kidney injury (AKI). In this case, the treatment may be delivered continuously while the patient is in bed. Haemodialysis is also used in otherwise healthy patients with End Stage Renal Disease (ESRD), who are living relatively normal lives. In this case, the treatment is delivered over a total of about 12-24 hours in 3-7 sessions per week (usually three sessions of four hours each per week).

These sessions are delivered while the patient is sitting in a chair, or overnight while the patient is asleep. The procedure is not painful or uncomfortable and does not require an anaesthetic. Haemodialysis requires trained operators, specialised equipment and supplies. It can be performed in a patient’s home. Transportable equipment is available.

The haemodialysis blood circuit

A dialysis machine pumps blood from the patient, through disposable tubing, through a dialyser, or artificial kidney, and back into the patient. Waste solute, salt and excess fluid is removed from the blood as it passes through the dialyser.

The dialysis machine also pumps a special fluid, the dialysis fluid, through a separate compartment in the dialyser. The blood and dialysis fluid are separated by a thin membrane, so they do not mix. Wastes pass through the membrane from blood into the dialysis fluid. Certain salts, required for health, may pass in the opposite direction, from dialysis fluid to blood. The ‘used’ dialysis fluid, carrying the wastes eventually flows into the drain.





The dialysis machine is controlled by an integral computer. In addition to pumping the blood, it prepares the dialysis fluid, monitors the system to ensure that the dialysate is continuously at the correct pressure, temperature and composition; so that blood flows­freely at the correct pressures and that no air has entered the blood. The dialysis machine also controls and monitors the removal of fluid by filtration (actually ‘ultrafiltration’ as explained later).

Haemodialysis requires up to 100 litres of dialysis fluid per treatment session (or up to 50 litres per day for continuous treatments). The dialysis fluid is sometimes provided in pre-prepared sterile bags. This allow the machine to be more compact (e.g. for portable systems or for bedside use in intensive care units). More commonly, the dialysis machine generates the dialysis fluid as required during treatment from connected supplies of purified water and concentrated salt and sugar solution.

To prevent transfer of blood-borne viruses between patients, and to simplify cleaning, the entire blood pathway (consisting of blood tubing, dialyser and any needles) is sterile, discarded after a single treatment. The dialysis machine itself can be used for multiple patients if cleaned between patients. The mechanical parts of the blood pump do not contact directly with the blood; they propel the blood along the tubing by squeezing the tube from outside using rollers. Similarly, the sensors which measure pressure in the blood at various points along the blood pathway are separated from the blood by multiple membranes; and, in some cases, an air gap, to prevent direct contact between blood and machine.

Objectives of Haemodialysis

Haemodialysis is the default treatment for patients with ESRD. Short-term objectives are to:

  • Correct electrolyte balance
  • Correct metabolic acidosis
  • Correct fluid state
  • Remove toxins

Longer-term objectives are to:

  • Optimise the patients functional status
  • Control BP
  • Prevent uraemia and its complications
  • Improve survival


Key point: currently, over 2 million people worldwide receive haemodialysis. As in the rest of the world, the number of patients receiving haemodialysis in the UK is increasing. According to the UK Renal Registry, in the UK, at the end of 2009, there were 49, 080 patients receiving renal replacement therapy (RRT) – 48% of these were renal transplant patients, and 44% were haemodialysis (HD) patients (23% Hospital HD, 20% Satellite HD, 1% Home HD), and 8% on peritoneal dialysis (Steenkamp, 2010).

The median age of prevalent patients was 57.7 years (HD 65.9 years, PD 61.2 years and transplant 50.8 years).

Key point: although transplantation is preferred, haemodialysis will continue to be the commonest form of non-transplant renal replacement therapy. Although it is a successful life-saving and life-sustaining therapy, the technique only partially replaces one aspect of renal function, ie water and solute excretion; and provides approximately 5% GFR. Consequently life expectancy is still significantly reduced.

Key point: mortality rates are high, but prolonged survival on dialysis is possible.



Iron (IV)

  • Venofer® iron sucrose; 100 mg/5ml
  • Cosmofer® iron dextran; 100 mg/2ml, 500 mg/10ml
  • Ferrinject® ferric carboxymaltose; 100 mg/2ml, 500 mg/10ml
  • Monofer® iron(III) isomaltoside 1000; 100 mg/ml
  • Rienso® ferumoxytol 30 mg/ml
  • Prescribe by brand

Iron (Oral)

  • Ferrous sulphate 200 mg (60 mg iron)
  • Ferrous gluconate (35 mg)
  • Ferrous fumarate 210 mg (68 mg)


  • Lanthanum carbonate (hydrate) is a non-calcium, non-aluminium containing phosphate binding agent
  • Fosrenol®: Tablets: 500mg, 750mg and 1g; Oral powder sachets: 750mg and 1g

Lupus Nephritis

Lisa Willcocks and Menna Clatworthy - Review Date March 2017

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterised by the presence of autoantibodies to a variety of self-antigens, and the formation of IgG immune complexes which become deposited in tissues. Both the severity and location of immune complex deposition can vary widely between individuals, with corresponding heterogeneity in clinical presentation. Up to half of patients with SLE will develop renal involvement (lupus nephritis), which has a variable presentation, including low grade proteinuria and haematuria, nephrosis, slowly progressive chronic kidney disease and rapidly progressive glomerulonephritis.

In the UK, systemic lupus erythematosus (SLE) has a prevalence of 10-50 per 100,000 in Caucasians, but is more common in people of Afro-Caribbean and southeast Asian ethnicities (Danchenko, Satia et al. 2006). The disease predominantly affects women under the age of 40 years (female:male ratio of 10:1).

Overt renal disease occurs in at least one-third of patients with SLE and is the most common severe manifestation. The development of nephritis is closely linked to survival and morbidity; 10–20% patients with lupus nephritis die within 10 years and a further 10–25% reach end-stage kidney disease (ESKD). However, there is considerable variation in severity, course and outcome. Lupus nephritis usually responds to corticosteroid and immunosuppressive therapy, but the toxicity of these drugs also contributes to morbidity and mortality.

Methoxy polyethylene glycol-epoetin beta (Mircera®)

  • Injection: Mircera®, prefilled syringe 30, 50, 75, 100, 120, 150, 200, 250, 360 micrograms


  • Anti-proliferative immunosuppressant
  • 250 mg caps, 500 mg tabs, oral suspension (1g/5ml), Injection 500mg.
  • Mycophenolate mofetil does NOT need to be prescribed by brand
  • Intravenous and oral doses are equivalent
  • Do NOT switch between mycophenolate mofetil (MMF) and mycophenolic acid (1g=720mg)
  • Mycophenolate sodium (Mycophenolic acid):180 mg or 360 mg tablets as Myfortic®

Nephrotic Syndrome

Peter Topham & Richard Glassock  -  Review Date Nov 2015 (Senior Editor Pete Topham)

Key Point: A urinary protein:creatinine ratio (UPCR) of >300 mg/mmol Cr (>3000 mg P/gm Cr) in a 'spot' morning urine sample is usually taken as 'nephrotic-range proteinuria' in an adult.

Key Point: Nephrotic Syndrome (NS) is not a specific disease and is defined biochemically by the presence of persistent 'nephrotic-range' proteinuria and hypoalbuminaemia (<30 g/L). Oedema is variably present.

Nephrotic syndrome is not a disease. It is a description of group of associated clinical features and laboratory abnormalities. These include abnormalities of liver metabolism, including excess synthesis of fibrinogen by the liver; and alterations in hepatic lipid synthesis and turnover. Many patients will have hypercholesterolaemia, and (initially) normal renal function. Other important complications are venous thrombosis, infection, and malnutrition (negative nitrogen balance)..
In the kidney there is damage to the glomerular filtration barrier which allows the passage of proteins, that are normally not filtered by the glomerulus, from the blood into the urine. This loss of protein lowers blood protein (and albumin) levels.

Retention of sodium and water occurs and results in oedema. This is due to alterations in distal tubule (and collecting duct) function which leads to increased renal avidity for sodium chloride. This process is discussed further in the Pathophysiology sections (below).

Nephrotic syndrome is a common reason for admission to a renal unit. It has many underlying causes, but the risks to the patient, and the general management, are broadly similar irrespective of the underlying cause.

Overall, NS is generally more common in adults; only minimal change disease is more common in children. The diagnosis is based on the presence of nephrotic range proteinuria; combined with history, physical examination, serological testing, and usually a renal biopsy. The treatment and prognosis depend on the cause.

Pathophysiology of Nephrotic Syndrome


Hypoalbuminaemia is predominantly due to urinary losses of protein, although a contribution from protein catabolism by tubular epithelial cells may also be relevant. White bands in the nails (Muehrcke's bands) are a characteristic sign of hypoalbuminaemia.

In response, hepatic albumin synthesis in increased but is insufficient to prevent the fall in serum albumin concentration. The increase in hepatic protein synthesis is non-specific and therefore the concentrations of proteins that are not lost in the urine may actually increase in nephrotic patients. This leads to some of the other consequences of NS including hypercholesterolaemia and hypercoagulability.


Nephrotic range proteinuria is almost invariably due to glomerular disease. Under normal circumstances the passage of most plasma proteins (particularly albumin) into the urine is prevented by the glomerular capillary wall (GCW).

The GCW is a trilaminar structure comprised of fenestrated glomerular endothelial cells, the glomerular basement membrane (GBM), and podocytes. It is richly decorated throughout with an anionic glycocalyx which electrostatically repels negatively charged proteins. In addition, the structure of the GBM and the podocyte intercellular junctions (slit-diaphragms) restricts the passage of proteins according to molecular size.

Proteinuric disease is usually associated with structural or functional changes in the GCW. In particular, it is now recognised that most nephrotic diseases are associated with podocyte injury and dysfunction (manifest on electron microscopy as foot process effacement), and the loss of anionic charge in the glomerular capillary wall. Thus proteinuria usually results from a loss of both charge and size selectivity in the GCW.

The precise mechanism underlying these changes is unknown for most diseases; but in inflammatory conditions, a variety of cytokines, eicosanoids, and complement components (eg C5b-9, TNF-alpha, interleukin-1β) may be implicated.

Haemodynamic changes in the glomeruli induced by angiotensin II and noradrenaline may also promote proteinuria. Experimentally, an increase in intraglomerular pressure results in proteinuria; and the corollary of this is, that currently available antiproteinuric therapies work through reducing intraglomerular pressure.

The precise mechanisms involved in the various diseases that are associated with nephrotic range proteinuria vary widely. Antibody-mediated, immune-complex-mediated, complement-mediated and cell-mediated processes have all been implicated in the primary forms of the clinical disorder.

In Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis  (FSGS), evidence suggests that circulating cells (T-cells and other) may secrete permeability factors; or alternatively down-regulate an inhibitor of permeability factor in response to unidentified etiologic agents.  In Membranous Nephropathy, immune complexes are formed in situ by reaction of a circulating auto-antibody (anti-phospholipase A2 receptor antibody) and its relevant auto-antigen on podocytes.

Other possible factors include: hereditary defects in proteins that are integral to the slit diaphragms and GBM of the glomeruli; activation of complement leading to damage of the glomerular epithelial cells; and loss of the negatively charged groups attached to proteins of the GBM and glomerular epithelial cells.

Haraldsson (2008) has reviewed the properties of the GBM, and mechanisms of proteinuria. And, in 2009 Machuca et al reviewed molecular and clinical findings in the field of genetics of NS, providing a better understanding of the complex physiology of the glomerular filtration barrier.


Oedema is thought to result from two distinct mechanisms:

Underfill Model
This is thought to be more common in children. The reduced plasma oncotic pressure promotes the translocation of fluid from the vascular compartment into the extracellular fluid compartment. The reduction in plasma volume stimulates both activation of the renin-angiotensin-aldosterone system, and release of vasopressin, which results in sodium and water reabsorption in the distal nephron. Capillary hydrostatic pressure is increased and this promotes further fluid movement into the extravascular compartment.

Overfill Model
This results primarily from a defect of sodium excretion in the distal nephron. The cause of the natriuretic defect is unclear but may relate to the tubulointerstial inflammation that often accompanies proteinuria. Sodium retention results in an increased blood volume associated with suppressed vasopressin and angiotensin/aldosterone levels. The increased intra-capillary hydrostatic pressure and the low oncotic pressure favours movement of fluid into the extravascular compartment.

In addition, sodium retention that accompanies the reduced GFR in patients with CKD and/or AKI can also contribute.

These mechanisms are discussed in more detail by Humphreys (1994), Kooman (2003) and Rondon-Berrios (2011).


Unlicensed product - ORTHOCLONE® OKT3.

5mg total in a 5ml ampule.
Administer by bolus IV injection in less than 1 minute.

Once opened, use immediately.

Peritoneal Dialysis

Lisa Crowley and Martin Wilkie  -  Review Date Jan 2016 (Senior Editor Andy Stein)

PD­is (predominantly) a home based therapy for patients with end-stage renal disease, and is reliant on the patients' own peritoneal membrane acting as the dialysis membrane. It has the advantage of allowing patients more independence in managing their own disease; and has benefits in terms of quality of life (Thong, 2008). It is often an excellent first choice for patients starting dialysis, particularly when they still have some native renal function (Chaudhary, 2011). PD regimes are designed on a much more individualised basis than patients on HD.

While the fluid is in situ, solutes move from the patients blood, across the peritoneal membrane, down the concentration gradient into the dialysate fluid. An osmotic gradient is created by high concentration of glucose (occasionally amino acid or glucose polymer solutions are used) in the dialysate fluid, which removes water from the patient. Acid-base balance is regulated by the absorption of lactate or bicarbonate (or combinations) from the dialysis fluid.

Clearance of urea and creatinine by PD is dependent on the­volume of dialysate drained at the end of a session. Clearance can be maximised by increasing the volume of the fluid exchanged and by ensuring the exchange time is optimised to allow equilibration between plasma solute concentrations and the dialysate. Water removal is adjusted by altering the dialysis dwell time and by altering the glucose concentration of the dialysate.

The latest ISPD guidelines can be found here and the Renal Association here.

Types of PD

Peritoneal dialysis is a technique whereby infusion of dialysis solution into the peritoneal cavity is followed by a variable dwell time and subsequent drainage. Ansari (2011) has reviewed the use of PD in AKI, but it is more commonly used to treat advanced CKD. There are several types:

Continuous ambulatory peritoneal dialysis (CAPD)
This is a continuous treatment usually consisting of four to five dialysis exchanges per day.­These are usually 2 litres. Exchanges are performed at regular intervals throughout the day, with a long overnight dwell. Diurnal exchanges last 4 to 6 hours, and the nocturnal exchange remains in the peritoneal cavity for 6 to 8 hours.

Automated­peritoneal dialysis (APD)
This is a continuous treatment carried out with an automated cycler machine. Multiple short-dwell exchanges are performed at night. 10-12L are usually exchanged, over 8-10 hours. There are lifestyle advantages to this technique, ie it leaves the daytime free. It can also be used to increase the dose of dialysis, or water removal in certain patient groups.

Tidal peritoneal dialysis
The cycler is programmed to leave a percentage of the preceeding dwell in the peritoneal cavity before the next­fluid instillation during night-time cycles. So the­peritoneal cavity­is never free of­fluid. It is useful for patients with abdominal pain between cycles, and those with frequent 'low drain' alarms overnight; but generally does not improve clearances, which was the original aim of its development.

Suitability for PD

Most patients will be suitable for PD catheter insertion, however it may be contraindicated in the following patients:

  1. BMI. Morbidly obese patients may be unsuitable, but many overweight patients are managed on PD very successfully
  2. Previous abdominal surgery and diverticular disease. This can­cause intra-abdominal adhesions and make insertion of the catheter technically difficult or impossible
  3. Abdominal stoma
  4. Abdominal/inguinal hernias. Will need repairing if the patient would like PD
  5. The patient (or relative) will need to be able to manage the technical aspects of PD

Advantages of PD

PD may be associated with better preservation of residual renal function (RRF). This may account for better early outcomes on PD compared to HD (Jansen, 2002; Moist, 2000).In 2006, Vonesh and colleagues concluded that survival on PD is equal if not better than survival on HD in non-diabetic and younger diabetic patients.

Key point: in PD, residual renal function may be better preserved than in HD.

Initial PD use preserves possible sites for vascular access for later in the patient's 'renal career'. There is some evidence that suggests initial treatment with PD, then subseqent transfer to HD, has­a superior outcome to a single dialysis modality. There is little evidence that PD leads to better longterm­outcomes when compared directly to HD. Studies that suggest that this true, usually do not take comormidity into account­(Miskulin, 2002).

Epidemiology and Outcomes

According to the Renal Registry (Steenkamp, 2010), there were 49,080 adult patients receiving RRT in the UK in 2010, equating to a UK prevalence of 794 pmp (64 pmp on peritoneal dialysis). Transplantation was the most common treatment modality (48%), HD was used in 44% and PD in 8% of RRT patients.

The age adjusted 1 year survival for patients on PD in 2007 was 94.5%, compared to 87.3% for patients on HD, continuing the trend in improvement on preceding years. These figures do not take into account the relative co-morbidities of the two patient groups; and in these patients outcome is determined more by co-morbidity than modality.


  • Tablets: plain 1 mg, 5 mg or 25 mg; enteric coated 2.5 mg or 5 mg,; soluble 5 mg tablets
  • Prednisolone 5 mg ≈  hydrocortisone 20 mg ≈ methyprednisolone 4 mg ≈ dexamethasone 750 micrograms

Renal Angiogram

James Ritchie and Lance Dworkin  -  Review Date Nov 2015 (Senior Editor Andy Stein)

Key point: contrast angiography remains the 'gold standard' for the investigation of atherosclerotic renovascular disease (ARVD). This can occur in the native or transplant kidney.

Renal angiography is not the first line investigation for ARVD. Because of its invasive nature, with attendant risks, indirect techniques such as CTA, MRA, duplex US are first line diagnostic techniques for ARVD. Rountas (2007) has reviewed the sensitivity and specificity of these techniques.

In the native kidney, less than 50% narrowing does not normally lead to renal hypoperfusion. Even then, renal oxygenation is preserved (Gloviczki, 2010); which is also surprising. It is not known whether the transplant kidney is similarly robust. Because of the importance of maximising transplant function, lower levels of arterial narrowing are usually looked for, and treated.

The conventional angiogram is superior to digital angiography but requires higher doses of contrast medium. Digital subtraction angiography (DSA) requires computer reconstruction to generate images.

It has several signficant limitations:

  1. Provides only 2D images
  2. No functional information. Although conventional angiography can detect the anatomical presence of a renal artery lesion, it does not provide data on its physiological or haemodynamic significance
  3. Invasive technique, with significant Complications (discussed later)
  4. Contrast nephropathy

Contrast nephropathy is the third leading cause of hospital acquired renal failure and is associated with significant morbidity and mortality.

Dworkin and Cooper published an excellent review article in 2009.

Indications for Angiography

This is an area of considerable debate that will be covered in the chapter on ARVD. Most would agree that the following are indications for angiography:

  1. Key point: to confirm the presence of ARVD in the native (or transplant) kidney at the time of a revascularisation procedure. Angiography is normally only performed when there is an established diagnosis of ARVD and a clear indication for revascularisation.
  2. Unexplained macroscopic haematuria, thought to be due to arteriovenous malformation.

General Points (should we be looking for ARVD?)

Most of this chapter concerns patients with atherosclerotic RVD.  Patients with fibromuscular dysplasia are younger and healthier generally and the complication rate is lower.

Also. There is considerable debate of whether we should be looking for atherosclerotic RVD at all. Based on the current literature, most practitoners, including sensible interventionalists, would agree that there is no reason to be looking for ARVD in medically stable patients. These investigations should be reserved for patients that are failing medical therapy.

Although not established as beneficial for any group, it is still rational to consider diagnosing and treating ARVD in patients that have:

  1. uncontrolled hypertension despite a maximal medical regimen (emphasis on maximal)
  2. declining kidney function (but not those with stable function)
  3. (perhaps) severe CHF with recurrent hospitalisations (but not those with stable CHF, or those with CHF but not on a good medical regimen)
  4. 'flash' pulmonary oedema

Renal Angiogram (showing a proximal RAS)






















Renal Biopsy

Lisa Crowley, Kieron Donovan, Peter Topham  -  Review Date Jan 2016 (Senior Editor Pete Topham)

Since its introduction to clinical medicine in the 1950s, percutaneous renal biopsy has become a routine investigation in the evaluation of patients with kidney dysfunction. It provides a tissue diagnosis in more than 95% of cases, and is a relatively safe procedure with a life-threatening complication rate of less than 0.1%. However, the decision to proceed to biopsy should not be taken lightly and must be made by a consultant. It is important that trainees discuss the need for a biopsy with a consultant before booking it.

Aim of Renal Biopsy

Patients with renal disease often present with a ‘syndrome’ – such as nephrotic syndrome, AKI, or CKD. In themselves, these are not ‘diagnoses’. They are merely patterns of kidney disease that can have many causes.To aid the management of such patients, the histological analysis of a renal biopsy sample should therefore aim to:

  • identify a specific diagnosis
  • reflect the level of disease activity
  • provide information to allow informed decisions about treatment.

Is the Biopsy Necessary?

This is a vital question to ask oneself at all stages of the process; as it is always a judgement of the balance of risk vs useful information. A renal biopsy is not without risk therefore before undertaking a biopsy, think carefully about whether the biopsy result is likely to alter management. Given the complexity of renal pathology, a discussion between the pathologist and the nephrologist is required, in order for the result to interpreted correctly within the clinical context.

The information gained subsequently affects management in approximately 30-40% of cases, and 85% of patients with nephrotic syndrome and unexplained AKI (Richards 1994, Stratta 2007). Nonetheless, at times, the role of renal biopsy has been debated (Madaio 1990, Adu 1996).

Most nephrologists would agree that renal biopsy is more likely to change management in symptomatic kidney disease (proteinuria, nephrotic syndrome), unexplained AKI or sudden changes in eGFR in CKD.  It can also be useful for prognostic purposes, as well as helping to direct or change treatment.

In nephrotic syndrome and AKI, the biopsy may make the difference between giving immunosuppression or not, withdrawal of drugs or not etc. The role of renal biopsy in determining the quantity and intensity of treatment is widely but not universally accepted, particularly in lupus nephritis.


There are four common indications for renal biopsy:

  • Significant proteinuria/nephrotic syndrome (>1g/L, or PCR > 100mg/mmol) with two normal sized, non-obstructed, kidneys and no obvious cause (usually considering the diagnosis of a glomerulo- or interstitial nephritis)
  • Acute Kidney Injury (AKI) with two normal sized, non-obstructed, kidneys and no obvious cause
  • Chronic Kidney Disease (CKD) with two normal sized, non-obstructed, kidneys and no obvious cause
  • Renal transplant dysfunction

Other, less common (and more controversial) indications. Many of these patients may have normal renal function:

  • Non-visible haematuria
  • Renal dysfunction in systemic disease (eg diabetes, myeloma, amyloidosis, SLE)
  • Familial renal disease (where diagnosis in this patient, benefits them and their family)


Biopsies are absolutely contraindicated in the following situation:

  • Uncontrolled bleeding diathesis

Biopsies are relatively contraindicated when:

  • Uncontrolled hypertension (>160/95)
  • Uncooperative patient
  • Patient unable to consent
  • Solitary kidney. This is a 'big decision' and should be carefully made by a consultant and the patient
  • Obstructed kidneys
  • Small kidneys (less than 10 cm; less than 9 cm in a small patient)
  • Anatomical abnormalities (eg vascular lesion)
  • Renal neoplasm, multiple cysts, abscess or pyelonephritis

Note: when considering a diagnosis of amyloid, it may be advisable to biopsy other less vascular tissues (fat, rectum) first, since this may establish the diagnosis and avoid the inherent risk of the renal biopsy. Patients with amyloid (particularly those with blood vessel deposition) may be more likely to bleed. This view has been challenged by Fish in 2010.

Diabetes and Renal Biopsy

If the clinical presentation is consistent with diabetic nephropathy (ie signficant proteinuria [often nephrotic range], CKD3b-4, diabetes of over 10 years duration, normal soluble immunology, presence of other microvascular complications [eg retinopathy and neuropathy]), renal biopsy is not necessary and it can be assumed that the patient has diabetic nephropathy.

If however the presentation is atypical (haematuria, haematoproteinuria, diabetes of less than 5 years duration, abnormal soluble immunology, no microvascular complications, rapid fall in GFR), renal biopsy should then be considered. Patients with diabetes may develop a glomerulonephritis or another form of intrinsic renal disease.  A higher than average risk of glomerulonephritis has been described in patients with diabetes (Soni, 2006) although this has not been universally seen (Waldherr, 1992).

Age, Race and Renal Biopsy

Moutzouris (2009) has published a series of biopsies in the elderly (> 80 years) suggesting this is still a useful technique with results that affect management in a significant number of patients.

There are racial differences between biopsy appearances. For example, Hoy (2012) has described a wide range of atypical findings in Australian aborginal people.

This talk by Vishal Golay (on 28.10.10) is a very good, especially regarding the practicalities of renal biopsy.

Renal Psychology

Carolyn Evans, Sarah Cook, Joanne Taylor  -  Review Date Jan 2016

Chronic kidney disease (CKD) is thought to occur in 14% of males, and 13% females; with 5% males, and 7% females having stages 3 – 5 CKD (Roderick et al, 2011). And, as the prevalence of CKD is higher in older people (Stevens et al, 2007), with an ageing population, the prevalence in the UK is likely to increase, as has been observed in the USA (Coresh et al, 2007).

Nephrologists are generally involved in patients with more advanced CKD (stages 3b – 5) and with those patients on renal replacement therapy. These patients often have multiple co-morbidities such as cardiovascular disease, hypertension, diabetes, renal bone disease and renal anaemia - so that medical management is challenging. Patients on renal replacement therapy may progress through periods on dialysis and transplantation with all their associated restrictions and complications.

Inevitably, because of the complexity of patient management, limited nursing and medical time is focussed on dealing with treatment related issues. Clinic appointments very rarely offer the time and opportunity to delve into the psychological impact of kidney failure, especially in patients on renal replacement therapy. Consequently, it is important to have services in place that can provide the appropriate adjunctive psychological assessment and interventions that CKD patients require.

The author was initially employed in early 2008 as the sole clinical psychologist in order to develop the service and this document outlines the five year development of psychological services within a rural county hospital, which is the hub for the provision of renal care in Dorset.



Renal Replacement Therapy on ICU

Nicholas Sangala and Marlies Ostermann  -  Review Date Jun 2016

Acute Kidney Injury (AKI) is a common complication of acute illness occurring in 13-18% of all hospitalised patients and up to 35% of patients in the Intensive Care Unit (ICU).­ It is associated with an increase in hospital mortality, length of stay, and is an independent risk factor for chronic kidney disease (CKD) including the need for long-term maintenance dialysis at discharge [1,2,3,4,5,6]. Renal replacement therapy (RRT) is not a cure for AKI, but is a supportive treatment that averts the immediate life threatening complications of AKI; whilst a diagnosis and definitive treatment is sought - and allows time for recovery of renal function following resolution of the original insult.­ Between 3-6% of critical care patients will require a period of RRT, and the in-hospital mortality, in this population of patients, is between 50-70% [7,8,9,10].­ Use of RRT on the ICU is therefore a relatively common occurrence, yet the evidence base on which intensive care physicians base their practice is varied in both quality and quantity. In this chapter we will review the latest guidance and the evidence base behind it.

Renal Transplant

Adnan Sharif  -  Review Date Feb 2016 (Senior Editor Paul Cockwell)

Kidney transplantation is the treatment of choice for the majority of patients with end-stage kidney disease. Since the first successful kidney transplant in 1954, the scientific advances over the subsequent decades have led to significant improvements in patient/graft survival and quality of life for kidney allograft recipients, making kidney transplantation one of the success stories of modern medicine. However with increasing success comes increasing expectations and major challenges remain in trying to expand, improve and optimise the option of kidney transplantation to all suitable candidates.

Survival data

The latest data from the NHS Blood and Transplant annual activity report 2010/2011 demonstrates the following patient survival data; living donors (1-year 99%, 5-year 96% and 10-year 90%), donation after brain death (1-year 96%, 5-year 89% and 10-year 74%) and donation after cardiac death (1-year 95%, 5-year 88% and 10-year 66%). Respective graft survival data is; living donors (1-year 97%, 5-year 92% and 10-year 79%), donation after brain death (1-year 94%, 5-year 84% and 10-year 69%) and donation after cardiac death (1-year 92%, 5-year 86% and 10-year 70%).

While these numbers represent excellent graft survival, and early graft losses has dramatically improved, concern remains over long term kidney allograft attrition rates which have remained relatively constant (Lodhi 2010). Understanding the mechanisms for long term kidney allograft loss is an important issue. El-Zoghby (2009) and colleagues have attempted to determine specific causes of kidney allograft loss and suggest glomerular pathology is the leading cause, with alloimmunity the most common mechanism leading to failure. However debate continues on the relative contributions between chronic antibody mediated injury  (Matas 2011) and calcineurin inhibitor nephrotoxicity (Chapman 2011) with regards to long-term graft failure.

Disparity in supply and demand for kidneys

Other concerns remain regarding ongoing disparity in the supply and demand for kidneys and the new strategic plan from NHS Blood and Transplant will focus on ways to tackle this over the upcoming few years. Novel strategies to tackle donation rates are being tried to overcome donor shortages. Some countries (e.g. Spain, Austria) have adopted an 'opt out' system which presumes consent unless an individual has specifically chosen to opt out. Within the United Kingdom, recently Wales has given the go ahead for their own opt out system (BBC News 2013) and it will be interesting to see how their experience unfolds. Other countries have adopted even more novel strategies by attempting to tackle donor apathy by introducing a priority scoring system. Lavee 2012 have demonstrated a marked increase since the recent introduction of a priority scoring system, which gives priority to kidney candidates who have previously donated or who have been previous organ donation registrants for 3 years or more. A similar strategy has been proposed for the United Kingdom Sharif 2013, with an emphasis on the potential to boost organ donation from Black, Asian, Minority Ethnic (BAME) groups.

Benefits of kidney transplantation

Patient survival following kidney transplantation is better in comparison to age-matched individuals remaining on the transplant waiting list. In a landmark study, Wolfe 1999 and colleagues performed a longitudinal study of 228,552 patients with end-stage kidney disease receiving haemodialysis and compared survival between three groups; patients receiving a transplant (n=23,275), wait-listed patients (46,164) and remaining patients not deemed fit for transplantation and continuing on dialysis. Mortality was 68% lower for transplant recipients than for those remaining on the transplant waiting list. This resulted in a mean increase in projected survival of 10 years. The increased survival benefit was seen in both sexes, all age group and in patients with diabetes. Larger benefits were seen in dialysis patients who were younger, white and young with diabetes.

While the findings from this study were replicated in a smaller study from Scotland (Oniscu 2005), more recent data from the UK Renal Registry 2012 report suggest kidney allograft recipients aged over 65 may not enjoy a major survival advantage compared to matched patients on the waiting list.

However there are other advantage of kidney transplantation that are equally important such as quality of life (Fiebiger 2004) that should always be factored into the decision to proceed with transplantation for each individual candidate. In addition successful kidney transplantation is more cost effective than expensive dialysis (Sharif 2011). The benefits and risks of kidney transplantation should be discussed on an individual basis with potential candidates. However for the majority of patients with end-stage kidney disease, kidney transplantation will be a more suitable modality of renal replacement therapy than dialysis.


  • Non-calcium, non-aluminium containing phosphate binding agent
  • Renagel® (sevelamer hydrochloride): 800 mg tablets
  • Sevelamer hydrochloride may cause metabolic acidosis, which can exacerbate secondary hyperparathyroidism and renal osteodystrophy (Brezina, 2004; De Santo, 2006; Barna, 2010). Sevelamar carbonate has been introduced to avoid this problem. Sevelamer carbonate is also licensed in pre-dialysis patients
  • Renvela® (sevelamer carbonate): 800 mg tablets and 2.4 g sachets of oral powder
  • Prescribe by brand


  • Immunsuppressive agent. An inhibitor of mammalian target of rapamycin (mTOR inhibitor)
  • Rapamune®: 0.5 mg, 1 mg and 2mg tablets; and 1 mg/ml oral solution
  • 0.5 mg tablets are not fully bioequivalent to higher strengths, so 2 x 0.5 mg is not equivalent to 1 x 1 mg

Supportive and Palliative Care

Christina Radcliffe and Sarah Yardley  -  Review Date Jun 2016 (Senior Editor Sunil Bhandari)­

  1. Supportive and palliative care should be offered on the basis of patient need and symptom burden, regardless of prognosis or underlying diagnosis
  2. Advance care planning is crucial to good supportive and palliative care; and should take place alongside renal replacement therapy and other disease-modifying treatments
  3. Common symptoms to ask about include: pain, breathlessness, weakness and fatigue, anorexia, depression and distress secondary to functional limitations
  4. Patients on renal replacement therapy over the age of 80 with a WHO performance score of 3 or more do not have a clear survival advantage in comparison to those managed conservatively and have increased rates of hospitalisation
  5. Conservative management requires active correction of reversible pathophysiology alongside symptom management and support for patients and families
  6. Professionals should explore ways to work collaboratively with patients and families in shared decision-making and can make use of varied resources to facilitate this co-operation
  7. Patients can benefit from joint working between specialists in nephrology and palliative care
  8. Morphine and diamorphine are not recommended in CKD stage 5 without dialysis; alternative opioids are preferred according to required route and stage of illness. Alfentanil and fentanyl are the preferred option for injectable opioid analgesia in ESRD
  9. Haloperidol is the first line recommendation for nausea and vomiting; glycopyronium or hyoscine butylbromide for excessive respiratory tract secretions; and midazolam for terminal agitation
  10. Reduced doses and increased dosing intervals are both important for all drugs (and metabolites) that are renally excreted


  • Immunosuppressive agent. Calcineurin Inhibitor
  • Prograf® - a twice daily preparation; capsules 0.5 mg, 1 mg, 5 mg; IV infusion 5 mg/ml
  • Advagraf® - a slow release once daily preparation
  • Also available as Vivadex®, Adoport®, Tacni® - all twice daily preparations. Modigraf® granules for oral suspension - twice daily
  • Prescribe by brand. Do not switch between brands


  • Valganciclovir is a prodrug of ganciclovir
  • 450 mg tablets, 50 mg/ml oral solution