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This Guidelines summary provides clinical guidance for primary care on the management of glomerular diseases in people of all ages. The full guideline has been separated into a series of summaries, as follows:

This summary covers general principles for the management of glomerular disease. For further recommendations and good practice points, see parts 2 and 3.

This summary consists of recommendations and practice points. Recommendations are presented in bold. Within each recommendation in this summary, the strength of the recommendation is indicated as level 1 (recommended) or 2 (suggested), and the quality of the supporting evidence is shown as A (high), B (moderate), C (low), or D (very low)—further information can be found on page 14 of the full guideline. 

For a complete set of recommendations and practice points, refer to the full guideline.

KDIGO=Kidney Disease: Improving Global Outcomes

View this summary online at guidelines.co.uk/456719.article

Kidney biopsy and kidney function

Kidney biopsy

  • The kidney biopsy is the ‘gold standard’ for the diagnostic evaluation of glomerular diseases; however, under some circumstances, treatment may proceed without a kidney biopsy confirmation of diagnosis (see Algorithm 1)
  • Repeat kidney biopsy should be performed if the information will potentially alter the therapeutic plan or contribute to the estimation of prognosis.

Algorithm 1: Considerations for kidney biopsy in patients with proteinuria and/or glomerular haematuria

alg 1 considerations for kidney biopsy v2.1

Assessment of kidney function

  • Obtain 24-hour urine collection to determine total protein excretion in patients with glomerular disease for whom initiation or intensification of immunosuppression is necessary, or who have a change in clinical status
  • For paediatrics, 24-hour urine collection is not ideal, as it may not be accurate and is cumbersome to collect; instead, monitor first morning protein–creatinine ratio (PCR)
  • Random ‘spot’ urine collections for PCR are not ideal, as there is variation over time in both protein and creatinine excretion
  • First morning urine collections may underestimate 24-hour protein excretion in orthostatic proteinuria
  • When feasible, a reasonable compromise is to collect an ‘intended’ 24-hour urine sample and measure PCR in an aliquot of the collection
  • There is no need to simultaneously and routinely quantify sodium excretion on each timed urinary collection, unless there is reason to suspect a failure to adhere to suggestions regarding dietary sodium restriction (see Table 1 and Practice Points 1.4.2 and 1.5.9 in the full guideline)
  • Quantify proteinuria in glomerular disease, as it has disease-specific relevance for prognosis and treatment decision-making; qualitative assessment of proteinuria may be useful in selected instances
  • In children, quantify proteinuria, but goals of treatment should not be different between disease aetiologies—a PCR of less than 200 mg/g (less than 20 mg/mmol) or less than 8 mg/m2/hour in a 24-hour urine should be the goal for any child with glomerular disease; acceptance of a baseline higher than this should come only with kidney biopsy evidence of kidney scarring
  • The Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) creatinine equation is preferred in adult patients with glomerular disease, and the modified Schwartz equation is preferred in children; the Full Age Spectrum (FAS) equation may be used in both adults and children (see Table 1).

Table 1: Assessment of kidney function in glomerular disease

Direct measures of kidney functionIndirect measures of kidney function: estimating equationsLimitations
  • Creatinine clearance

    • 24-hour urine creatinine

  • eGFR

  • No estimate of kidney function has been specifically validated for glomerular disease and/or nephrotic syndrome

  • Ethnicity is often a confounding influence

  • In creatinine-based formulas, hypoalbuminaemia may lead to overestimation of true GFR due to increased tubular creatinine secretion

  • Glucocorticoids may increase serum cystatin C, potentially underestimating eGFR

  • Low muscle mass overestimates eGFR using creatinine-based formulae

  • AKI confounds all estimates, which are valid only in steady state

  • Measured GFR[A]

    • insulin clearance (gold standard)

    • radioisotopic plasma clearance

      • 125 iothlamite

      • 99m Tc-DTPA

      • 51 Cr-EDTA

  • non-radioisotopic plasma clearance

    • iohexol


  • Cockroft–Gault (140-age) (weight [kg]) x 0.85, if female/serum creatinine (mg/dl) x72

  • MDRD equations (not valid for eGFR >60 ml/min/1.73 m2)

  • CKD–EPI creatinine equation (preferred) (valid with eGFR >60 ml/min/1.73 m2)

  • CKD–EPI–cystatin C equations (valid for eGFR >60 ml/min/1.73 m2)

  • FAS equation (valid even in eGFR >60 ml/min/1.73 m2)


  • Schwartz equation and its modifications

  • FAS formulae

Abbreviations: AKI=acute kidney injury; CKD–EPI=Chronic Kidney Disease Epidemiology Collaboration; 51 Cr-EDTA=chromium-51 labelled ethylenediamine tetraacetic acid; 99m  Tc-DTPA=diethylene-triamine-pentaacetate; eGFR=estimated glomerular filtration rate; FAS=full age spectrum; GFR=glomerular filtration rate; MDRD=modification of diet in renal disease

[A] In ml/min/1.73 m2. The correction coefficient for race in GFR estimating equations is controversial, and discussions about this topic are ongoing. Refer to the KDIGO CKD guideline for more information.

Evaluation of haematuria

  • Routine evaluation of urine sediment for erythrocyte morphology and the presence of red cell casts and/or acanthocytes is indicated in all forms of glomerular disease
  • Monitoring of haematuria (magnitude and persistence) may have prognostic value in many forms of glomerular disease; this is particularly applicable to immunoglobulin (Ig) A nephropathy (IgAN) and IgA vasculitis (IgAV; see Chapter 2 of the full guideline).

Oedema management in nephrotic syndrome

Table 2: Oedema management in nephrotic syndrome

Use loop diuretics as first-line therapy for treatment of oedema in the NS

  • Twice-daily dosing preferred over once-daily dosing; daily dosing may be acceptable for reduced eGFR

  • Increase dose of loop diuretic to cause clinically significant diuresis or until maximally effective dose has been reached

  • Switch to longer-acting loop diuretic such as bumetanide or torsemide/torasemide if concerned about treatment failure with furosemide, or if concerned about oral drug bioavailability

Restrict dietary sodium intake

  • Restrict dietary sodium to <2.0 g/day (<90 mmol/day)

Use loop diuretics with other mechanistically different diuretics as synergistic treatment of resistant oedema in the NS

  • All thiazide-like diuretics in high doses are equally effective. None is preferred

  • Thiazide diuretics, administered with an oral or IV loop diuretic, will impair distal sodium reabsorption and improve diuretic response

  • Amiloride may provide improvement in oedema/hypertension, and counter hypokalaemia from loop or thiazide diuretics

  • Acetazolamide may be helpful for the metabolic alkalosis of diuresis

  • Spironolactone may provide improvement in oedema/hypertension, and counter hypokalaemia from loop or thiazide diuretics

Monitor for adverse effects of diuretics

  • Hyponatraemia with thiazide diuretics

  • Hypokalaemia with thiazide and loop diuretics

  • Impaired GFR

  • Volume depletion, especially in paediatric/elderly patients

  • Hyperkalaemia with spironolactone and eplerenone, especially if combined with RAS blockade

Strategies for diuretic-resistant patients

  • Amiloride

  • Acetazolamide

  • IV loop diuretics (bolus or infusion) alone

  • IV loop diuretics in combination with IV albumin

  • Ultrafiltration

  • Haemodialysis

  • Amiloride may reduce potassium loss and improve diuresis. Acetazolamide may help to treat metabolic alkalosis but is a weak diuretic

Abbreviations: eGFR=estimated glomerular filtration rate; GFR=glomerular filtration rate; IV=intravenous; NS=nephrotic syndrome; RAS=renin—angiotensin system

Hypertension, proteinuria, and hyperlipidaemia in glomerular disease

Table 3: Management of hypertension and proteinuria reduction in glomerular disease

Use ACEi or ARB to maximally tolerated or allowed dose as first-line therapy in treating patients with both hypertension and proteinuria

  • Do not stop ACEi or ARB with modest and stable increase in serum creatinine (up to 30%)

  • Stop ACEi or ARB if kidney function continues to worsen, and/or refractory hyperkalaemia

  • Combinations of ACEi and ARB may be used in young adults without diabetes or cardiovascular disease, but benefits and safety are uncertain

  • Caveat: do not start ACEi/ARB in patients who present with abrupt onset of NS. These drugs can cause AKI, especially in patients with MCD

Target systolic blood pressure in most adult patients is <120 mm Hg using standardised office BP measurement. Target 24-hour mean arterial pressure in children is ≤50th percentile for age, sex, and height by ambulatory blood pressure monitoring

  • Refer to KDIGO BP guideline

  • Formally speaking, SBP <120 mm Hg has not been validated in GN. In practicality, we are able to achieve an SBP of 120–130 mm Hg in most patients with glomerular disease

Uptitrate an ACEi or ARB to maximally tolerated or allowed daily dose as first-line therapy in treating patients with GN and proteinuria alone

  • Indicated for persistent proteinuria despite treatment of primary GN with immunosuppression (where indicated)

  • Avoid use of an ACEi or ARB if kidney function is rapidly changing

Proteinuria goal is variable depending on primary disease process; typically, <1 g/day

  • It may be reasonable to delay initiation of ACEi or ARB for patients without hypertension with podocytopathy (MCD, SSNS, or primary FSGS) expected to be rapidly responsive to immunosuppression

  • Proteinuria goal is disease-specific in adults with GN

Monitor labs frequently if on ACEi or ARB

  • Titration of ACEi or ARB may cause AKI or hyperkalaemia

Counsel patients to hold ACEi or ARB and diuretics when at risk for volume depletion

  • Increased risk for AKI and hyperkalaemia

  • Counsel patients according to level of education in a culturally sensitive manner

  • Consider transiently stopping RASi during sick days

Use potassium-wasting diuretics and/or potassium-binding agents to reduce serum potassium to normal, in order to use RAS blocking medications for BP control and proteinuria reduction 

Treat metabolic acidosis (serum bicarbonate <22 mmol/l)

  • Loop diuretics

  • Thiazide diuretics

  • Patiromer

  • Sodium zirconium cyclosilicate (each 10 g of sodium zirconium cyclosilicate contains 800 mg of sodium)

  • Supplement with oral sodium bicarbonate

Employ lifestyle modifications in all GN patients as synergistic means for improving control of hypertension and proteinuria

  • Restrict dietary sodium to <2.0 g/day (<90 mmol/day)

  • Normalise weight

  • Exercise regularly

  • Stop smoking

Intensify dietary sodium restriction in those patients who fail to achieve proteinuria reductions, and who are on maximally tolerated medical therapy Restrict dietary sodium to <2.0 g/day (<90 mmol/day). Consider using mineralocorticoid receptor agonists in refractory cases (monitor for hyperkalaemia)
Abbreviations: ACEi=angiotensin-converting enzyme inhibitor; AKI=acute kidney injury; ARB=angiotensin II receptor blocker; BP=blood pressure; FSGS=focal segmental glomerulosclerosis; GN=glomerulonephritis; KDIGO=Kidney Disease: Improving Global Outcomes; MCD=minimal change disease; NS=nephrotic syndrome; RAS=renin–angiotensin system; RASi=renin–angiotensin system inhibitors; SBP=systolic blood pressure; SSNS=steroid-sensitive nephrotic syndrome

Table 4: Management of hyperlipidaemia in glomerular disease

Treatment of hyperlipidaemia may be considered in patients with NS, particularly for patients with other cardiovascular risk factors, including hypertension and diabetes

High-quality data are lacking to guide treatment in these patients

Use lifestyle modifications in all patients with persistent hyperlipidaemia in glomerular disease:

  • heart-healthy diet

  • increased physical activity

  • weight reduction

  • smoking cessation

  • Not well studied as primary means of reducing lipids in NS

  • Can be used as primary therapy in low-risk individuals with mild-to-moderate hyperlipidaemia

  • Additive to pharmacological treatment of hyperlipidaemia

  • Considered first-line treatment of hyperlipidaemia in children

  • Consider a plant-based diet

  • Avoid red meat

Consider starting a statin drug as first-line therapy for persistent hyperlipidaemia in patients with glomerular disease:

  • assess ASCVD risk based on LDL-C ApoB, triglyceride and Lp(a) levels, age group, and ASCVD ‘risk enhancers’

  • align statin dosage intensity to ASCVD risk

  • statins can be initiated in children >8 years old with concerning family history, extremely elevated LDL-C or Lp(a), in the context of informed shared decision-making and counselling with patient and family


  • Reduced eGFR (<60 ml/min/1.73 m2 not on dialysis) and albuminuria (ACR >30 mg/g) are independently associated with an elevated risk of ASCVD

  • ASCVD risk enhancers include chronic inflammatory conditions such as systemic lupus erythematosus, rheumatoid arthritis, history of preeclampsia, early menopause, South Asian ancestry, CKD, and HIV/AIDS (accuracy of ASCVD risk estimators have not been well validated for adults with chronic inflammatory disorders or HIV)

  • Adherence to changes in lifestyle and effects of LDL-C lowering medication should be assessed by measurement of fasting lipids and appropriate safety indicators 4–12 weeks after statin initiation/dose adjustment or inflammatory disease-modifying therapy/antiretroviral therapy, and every 3–12 months thereafter, based on need to assess adherence or safety

Consider initiation of non-statin therapy in those individuals who cannot tolerate a statin, or who are at high ASCVD risk and fail to achieve LDL-C or triglyceride goals despite maximally tolerated statin dose:

  • bile acid sequestrants

  • fibrates

  • nicotinic acid

  • ezetimibe

  • PCSK9 inhibitor

  • lipid apheresis

  • Bile acid sequestrants have a high rate of GI side effects, limiting their use

  • Bile acid sequestrants and fibrates have been shown in small studies to reduce serum cholesterol in NS

  • Fibrates will increase serum creatinine level due to direct action on the kidney

  • Ezetimibe has limited vascular and clinical benefits, but is used in statin-intolerant patients as salvage therapy

  • Nicotinic acid and ezetimibe have not been studied in patients with NS

  • PCSK9 inhibitors may be beneficial in NS; trials ongoing

Abbreviations: ACR=albumin–creatinine ratio; Apo=apolipoprotein; ASCVD=atherosclerotic cardiovascular disease; CKD=chronic kidney disease; eGFR=estimated glomerular filtration rate; GI=gastrointestinal; LDL-C=low-density lipoprotein cholesterol; Lp=lipoprotein; NS=nephrotic syndrome; PCSK9=proprotein convertase subtilisin/kexin type 9

Hypercoagulability and thrombosis

  • Full anticoagulation is indicated for patients with thromboembolic events occurring in the context of nephrotic syndrome (NS); prophylactic anticoagulation should be employed in patients with NS when the risk of thromboembolism exceeds the estimated patient-specific risks of an anticoagulation-induced serious bleeding event (see Algorithm 2). 

For anticoagulant dosing considerations in patients with NS, see Box 1 and Algorithm 3.

Algorithm 2: Anticoagulation in nephrotic syndrome

alg 2 anticoagulation in nephrotic syndrome v3

Box 1: Anticoagulant dosing considerations in patients with nephrotic syndrome

Prophylactic anticoagulation during transient high-risk events

  • Low-dose anticoagulation (for example, unfractionated heparin 5000 U subcutaneous twice per day)
  • Low–molecular-weight heparin: dose reduction may be advised with a creatinine clearance of less than 30 ml/min (unadjusted for body surface area); avoid in kidney failure.

Full warfarin anticoagulation for thromboembolic events

  • Intravenous heparin followed by bridging to warfarin is preferred
  • Higher than usual heparin dosing may be required in NS due to antithrombin III urinary loss
  • Long-term experience with warfarin makes it the anticoagulant of choice until pharmacokinetic studies are performed with newer agents
  • International normalised ratio (INR) should be monitored frequently, since warfarin–protein binding may fluctuate with changing serum albumin
  • Target INR is 2–3
  • These recommendations are not supported by randomised controlled trials
  • Be watchful of interactions of warfarin with other medications.

Factor Xa inhibitors (Xai): not systematically studied in patients with NS

  • Dosing in the general population is adjusted according to serum creatinine, creatinine clearance, (estimated by Cockroft–Gault equation), age, and weight. Urinary clearance of the Xai varies:
    • apixaban: 27%
    • edoxaban: 50%
    • rivaroxaban: 66%
  • The effects of hypoalbuminaemia on drug dosing have not been studied, and these drugs are heavily albumin-bound, which is likely to substantially affect their half-lives
  • Protein-binding:
    • apixaban: 92–94%
    • edoxaban: 55%
    • rivaroxaban: 92­–95%
  • Despite a few favourable case reports, the pharmacokinetic properties of these drugs require additional study for both safety and efficacy before they can be generally recommended in nephrotic patients

Direct thrombin inhibitors (DTIs): not systematically studied in patients with NS

  • Dosing in the general population is adjusted according to creatinine clearance for dabigatran. No adjustment is required for argatroban. The urinary clearance of the DTI varies:
    • argatroban: 22% (6% metabolites; 16% unchanged drug)
    • dabigatran etexilate: 7%
  • The effects of hypoalbuminaemia on drug dosing have not been studied, and these drugs are modestly albumin-bound, which is likely to affect their half-lives
  • Protein binding:
    • argatroban: 54%
    • dabigatran etexilate: 35%
  • Despite improved safety in the general population, the pharmacokinetic properties of these drugs require additional study for both safety and efficacy before they can be recommended in nephrotic patients.

For recommendations and an algorithm on prophylactic anticoagulation in adults with glomerular nephropathy/nephrotic syndrome, refer to the full guideline.

Risks of infection

  • Use pneumococcal vaccine in patients with glomerular disease and NS, as well as patients with chronic kidney disease (CKD). Patients and household contacts should receive the influenza vaccine; patients should receive herpes zoster vaccination (Shingrix)
  • Screen for tuberculosis, hepatitis B virus, hepatitis C virus, HIV, and syphilis in clinically appropriate patients (see Chapter 7 of the full guideline)
  • Strongyloides superinfection should be considered in patients receiving immunosuppression who once resided in endemic tropical environments and who have eosinophilia and elevated serum Ig E levels
  • Prophylactic trimethoprim–sulfamethoxazole should be considered in patients receiving high-dose prednisone or other immunosuppressive agents (rituximab, cyclophosphamide).

Outcome measures

  • Goals for proteinuria reduction with treatment vary among the various specific causes of glomerular disease
  • A 40% or greater decline in eGFR from baseline over a 2–3-year period has been suggested as a surrogate outcome measure for kidney failure.

Pharmacological aspects of immunosuppression

For minimisation of immunosuppression-related adverse effects, see Figure 15 in the full guideline.

Dietary management in glomerular disease

Table 5: Dietary management in glomerular disease

Restrict dietary sodium to reduce oedema, control blood pressure, and control proteinuria 

  • Dietary sodium <2.0g/day (<90 mmol/day)

Restrict dietary protein based on degree of proteinuria

  • Nephrotic-range proteinuria: 0.8–1.0 g/kg/day protein intake[A]

  • Add 1 g per g of protein losses (up to 5 g/day)

  • The safety protein restriction of GN has not been established in children

  • Plant-based diets may be preferred

Restrict dietary protein based on kidney function

  • eGFR <60 ml/min/1.73 m2 with nephrotic-range proteinuria

  • Limit or target intake to 0.8 g/kg/day

  • Avoid <0.6 g/kg/day due to safety concerns and risk of malnutrition

  • Emphasis on vegetable (plant) sources of protein as appropriate

Restrict caloric intake to achieve normal BMI and limit central adiposity in order to reduce CKD progression, development of kidney failure, CV events, and mortality

  • Target caloric intake 35 kcal/kg/day

  • eGFR <60 ml/min/1.73 m2: 30–35 kcal/kg/day

Restrict dietary fats in patients with elevated serum cholesterol to prevent CV complications

  • Heart-healthy diet

  • Dietary fat <30% of total calories

  • Mono- or polyunsaturated fat 7–10% of total calories

Abbreviations: BMI=body mass index; CKD=chronic kidney disease; CV=cardiovascular; eGFR=estimated glomerular filtration rate; GN=glomerulonephritis

[A] Ideal body weight

Pregnancy and reproductive health in women with glomerular disease

  • Care for the pregnant patient with glomerular disease needs coordination between nephrology and obstetrics, and ideally, such planning should be considered before pregnancy.


Full guideline:

Kidney Disease Improving Global Outcomes. KDIGO 2021 Clinical practice guideline for the management of glomerular diseases. Kidney Int 2021; 100 (4S): S1–S276. Available at: kdigo.org/wp-content/uploads/2017/02/KDIGO-Glomerular-Diseases-Guideline-2021-English.pdf

Published date: October 2021.


Lead image: Rasi/stock.adobe.com 

KDIGO general management of glomerular diseases guideline