echogenicity.HIV-associated nephropathy (HIVAN)
Acute renal failure and HIV seroconversion
Kidney disease was relatively common before the ART era. Proteinuria may be found in up to 30%. Necropsy studies in the USA have shown renal pathological abnormalities in 3–7%. In the ART era 1° renal diseases, diabetes, hypertension, vascular disease, and drug toxicity (including antiretrovirals) are more common than HIV-associated nephropathy.
Initial presentation may be as acute renal failure, especially in advanced HIV disease, 2° to the following:
• Dehydration and electrolyte disturbances (e.g. following vomiting and diarrhoea).
• Acute tubular necrosis due to:
• drug nephrotoxicity (e.g. tenofovir, adefovir, aminoglycosides, pentamidine, aciclovir, cidofovir, foscarnet, amphotericin B)
• rhabdomyolysis can occur with use of statins in combination with PI.
• Obstruction (2° to nephrolithiasis and crystalluria):
• Nephrolithiasis—indinavir, rarely atazanavir.
• sulfadiazine and aciclovir—can cause crystalluria especially in high dosage and with dehydration.
HIV-related infection (e.g. TB) can involve the kidney.
The general management of renal failure should follow the same principles as for HIV –ve patients, i.e. fluid replacement, dietary restriction, renal replacement therapy, erythropoietin, vitamin D analogues, reducing dose of drugs, etc.
Address all risk factors such as smoking, hypertension, dyslipidaemia, hyperuricaemia, metabolic syndrome, vascular disease. The following should be measured routinely:
• Dipstick for protein in urine and, if +ve, quantify with 24-hour urine protein or urine spot sample for urine PCR (uPCR). 24-hour urine collection may not be reliable.
• Serum creatinine should be complimented by an estimated glomerular filtration rate (eGFR) using MDRD or Cockcroft–Gault equations. If uPCR >45 or eGFR <60, renal ultrasound and consider referral to nephrology (definitely if uPCR>100 mg/mmol); otherwise minimum annual measurements.
• Patients at high risk for development of renal dysfunction, i.e. HIV VL >4000 copies/mL, CD4 <200 cells/µL, black race, diabetes, HCV co-infection, or HBV, may need to have renal function monitored more frequently.
First described in 1984. Early studies from USA demonstrated that it accounted for >50% of HIV-related renal disease. Renal glomerular and tubular epithelial cells have been shown to be infected by HIV, although the mechanisms of viral-induced injury are unclear.
Predominantly found in black ♂ of African origin and, currently, the third most common cause of end-stage renal disease (ESRD) in 20–64-year-old African Americans. Low incidence amongst follow-up patients (0.25/1000 patient-years) and higher (1%) in newly diagnosed black people. 10:1 M:F ratio.
Presents with nephrotic syndrome—proteinuria (>3.5 g/day), hypo-albuminaemia, oedema, and hyperlipidaemia. Typically, no hypertension. Leads to progressive renal insufficiency, which is modified with ART.
• CD4 count usually <200 cells/µL.
• Urinalysis shows leucocytes, hyaline casts, and oval fat bodies, but no cellular casts.
• Renal ultrasound typically shows normal or enlarged renal size with echogenicity.
• Markedly impaired renal function.
• Renal biopsy may be required if diagnosis in doubt (e.g. patient with other risk factors for renal disease or not responding to ART). Definitive diagnosis is made by renal biopsy showing focal segmental glomerulosclerosis, collapse of glomerular tuft associated with tubular ectasia, and tubulo-interstitial nephritis.
• ART, with dose adjustment when GFR<50 mL/min, avoid nephrotoxic ART e.g. tenofovir, PI. Leads to >20% in creatinine clearance. 
need for renal replacement therapy.
• Prednisolone if not improving (improves renal function by HIV-initiated inflammatory process).
• Angiotensin-converting enzyme inhibitors, if initiated prior to severe renal insufficiency may offer long-term renal survival benefits. Angiotensin receptor blockers are alternatives.
• Transplant should not be withheld if clinically warranted.
Less common than HIVAN, but reported as the main cause of HIV-related renal disease in non-black races. Found in 10–80% of autopsy and biopsy studies in HIV +ve patients from different European and Asian countries. Most common form is membranoproliferative glomerulo-nephritis. Membranous nephropathy, post-infectious glomerulonephritis, fibrillary glomerulonephritis, and IgA nephropathy (majority Caucasians and Hispanics) are other described forms of immune-mediated renal disease.
HBV and HCV both more common in injecting IV drug users, are important co-infections and may individually cause renal disease.
HCV-associated cryoglobulinaemic glomerulonephritis is found in both HIV- and non-HIV-infected patients, but is more aggressive in the former. Typical presentation includes purpura, arthralgias, and peripheral neuropathy, Raynaud’s phenomena in addition to renal insufficiency.
HBV, syphilis, and malignancy may all cause membranous nephropathy, and are all found more frequently in those with HIV infection.
Slowly progressive and mild compared with HIVAN. Typical early features are asymptomatic proteinuria and microscopic haematuria, with mild renal insufficiency.
• Serum cryoglobulin measurement (blood collected must not be allowed to cool, generally kept warm in sand).
• Detection of other infection(s), e.g. syphilis, HBV, and HCV.
• Renal biopsy if required: membranoproliferative glomerulonephritis.
• Treat any co-infection or malignancy.
Appears to be the most common microvascular injury associated with HIV. May be associated with malignancy (lymphoma), other infections (herpes, CMV), or drugs (valaciclovir, circumstantial). Thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome occur, characterized by micro-angiopathic haemolytic anaemia with renal insufficiency, thrombocytopenia, fever, and neurological changes. Mean age at presentation 35 years with 80% males. Poor prognosis in HIV, with mortality of 66–100%. Investigations may show fragmented red cells on blood film, thrombocytopaenia, anaemia, bilirubin, LDH, renal dysfunction. Massive proteinuria is uncommon (unlike immune-mediated disease and HIVAN). ART and plasmapheresis are the mainstay of therapy. Steroids may be helpful. Splenectomy may be helpful in refractory cases.
Not uncommon and may be associated with other renal pathology, such as HIVAN. Equal prevalence in black and Caucasian people. May present with proteinuria, renal failure, or nephrotic syndrome. Acute interstitial nephritis related to allergic drug reactions presents with acute renal failure, skin rash, and eosinophilia. NSAIDs are a common cause.
Acute renal failure and nephrotic syndrome may be presenting features of acute HIV seroconversion. Renal biopsy typically shows acute tubular necrosis and mesangio-proliferative glomerulonephritis, with tubuloreticular inclusions.
• The overall incidence of severe renal dysfunction in patients taking anti-retrovirals is <1%.
• Indinavir: ~4% develop nephrolithiasis, prevented by ample fluid intake (>2 L/day). Nephrolithiasis reported with other PIs (e.g. atazanavir, 0.97% prevalence, high risk of recurrence).
• Ritonavir: interstitial nephritis.
• Tenofovir: far more common with TDF than TAF—renal tubular dysfunction with hypophosphataemia, normoglycaemic glycosuria, and proteinuria (late phenomenon). Fanconi’s syndrome may develop. Phosphate should be monitored monthly, then 3-monthly after 1 year.
• Dose adjustment is not necessary for PI and NNRTI, but most NRTI require dose adjustment (see Table 50.1) with renal dysfunction and creatinine clearance <60 mL/min. Need to split fixed-dose combinations.
Table 50.1 NRTI dose adjustments
| Antiretroviral | Dose adjustment | ||
| Protease inhibitors, NNRTI, integrase inhibitors, abacavir, and enfuviritide | No dose adjustment (fixed dose combinations need to be split) | ||
| Normal dose | eGFR | Dose | |
| Emtricitabine | 200 mg od | 30–49 | 200 mg 48-hourly |
| 15–29 | 200 mg 72-hourly | ||
| <15 or HD* | 200 mg 96-hourly | ||
| Lamivudine | 300 mg od | 30–49 | 150 mg 24-hourly |
| 15–29 | ×1 150 mg then 100 mg 24-hourly | ||
| 5–14 | ×1 150 mg then 50 mg 24-hourly | ||
| <5 or HD | ×1 50 mg then 25 mg 24-hourly | ||
| Tenofovir disoproxil fumarate | 300 mg od | 30–49 | 300 mg 48-hourly |
| 10–29 | 300 mg twice weekly (72–96-hourly) | ||
| <10 | No recommendation | ||
| HD | 300 mg every 7 days | ||
| Tenofovir alafenamide/ emtricitabine (Descovy®) | od | <30 | Not recommended |
| Tenofovir disoproxil fumarate/emtricitabine (Truvada®) | od | 30–49 | 1 tablet every 48 hours |
| <30 | Not recommended | ||
| Maraviroc | Differs depending on combination | <30 without CYP3A inducer/inhibitor | 300 mg bd |
| <30 with CYP3A inducer/inhibitor | Not recommended | ||
* HD, haemodialysis.
Dialysis should be considered (haemodialysis is currently the preferred method). May only be required on a temporary basis until ART is introduced. Cadaver renal transplantation has been performed with no evidence of rate of opportunistic infections or rejection.