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HIV related kidney disease: A growing problem

Based on a 2012 UNAIDS report, approximately 3.4 million people are living in Nigeria with HIV infection and in 2011 about 210,000 people died from the infection. Patients unable to access treatment for their HIV frequently end up with HIV related disease of the kidney in addition to other complications of HIV such as opportunistic infections like tuberculosis and pneumocystis pneumonia.  For patients able to consistently access effective anti-retrovirals therapy (ART) and care, life expectancy is prolonged by decades and effective in preventing and even treating HIV associated nephropathy (HIVAN). Prolongation of life from ART however, permits opportunities for other non-HIV diseases of the kidney which healthcare providers must be aware of and identify.  


HIV related kidney disease in Nigeria is estimated to be the cause of 10% or more of cases of kidney failure after diabetes, hypertension and herbal toxin nephropathies. In general, HIV associated kidney disease could be acute with causes similar to that of the non-HIV population or chronic largely due to focal sclerosis (classic HIVAN) but can also be due to other causes of chronic kidney disease

Causes of kidney dysfunction in patients with HIV infection can result from 1. Direct kidney infection with HIV 2. Adverse effects of anti-retroviral drugs on the kidney. 3. Dehydration from nausea, vomiting, poor appetite   4.  Common causes of acute renal failure similar to that of the non HIV population. 

Main means of HIV transmission in Nigeria include: 1. Sexual contact         2. Blood transfusion withinfected blood and blood products. 3. Materno-fetal transmission.          

HIV transmission due to illicit intravenous drug abuse is relatively low in Nigeria


PRESENTATION OF CLASSICAL HIVAN: 1. Nephrotic range (3+ or more) proteinuria. This translates to over 3.5 grams of protein in the urine per day. 2. Edema is often present especially in the Nigerian context. 3. Patients are HIV I or II seropositive, with a detectable viral load indicative of active viral replication. CD4 counts are usually <200 cells/mm3. 4. Ultrasound at early stages shows normal sized to enlarged kidneys that are echogenic (whiter than nearby liver) on ultrasound with loss of corticomedullary differentiation. The echogenicity may be seen even on CT scan images.  5. Other features in urinalysis include hematuria, oval fat bodies


Other presenting features of HIVAN. Interestingly, blood pressure is usually normal in cases of HIVAN. If blood pressure is elevated, it suggests other alternative or additional causes of renal impairment. Hyponatremia from a syndrome of inappropriate anti-diuretic hormone secretion and hyperkalemia can also be seen. 


Mechanism of HIVAN and risk factors for chronic kidney disease in HIV patients

Active viral replication in the renal tubules and glomerulus triggers release of substances  that initiate cell death signals that kill kidney cells. Diabetes, hypertension, older age, other viral infections such as hepatitis B and C as well as family history and ART can increase the risk for kidney disease in patients with HIV and complicate the clinical picture.

Causes of Acute Renal Failure in HIV

Dehydration, allergic interstitial nephritis, immune complex glomerulonephritis,  hemolytic uremic syndrome, obstructive uropathy from crystal induce renal failure, rhabdomyolysis and myoglobinuric renal failure


Truth about risk of kidney failure from ART

Most HIV medicines are well tolerated and not all side effects of these medicines result in kidney failure even though they might have effects on some function. When used and monitored properly ART's are more beneficial than harmful. 

 Nucleoside reverse transcriptase inhibitors (NRTI's) such as zidovudine, abacavir and lamivudine can present with type B lactic acidosis. Didanosine is also an NRTI and can cause low potasium, sodium and magnesium levels. Stavudine is also another NRTI can cause hyperuricemia. Non nucleoside reverse transcriptase inhibitors (NNRIT"S) generally do not have any kidney toxicity except for nevirapine than can cause lactic acidosis. NNRTI's and NRTI's require dose reduction for patients with significant kidney disease (creatinine clearance < 50 ml/min)

Protease inhibitors (PI's) like ritonavir or indinavir can cause kidney stones so patients should be sure to maintain hydration while on such therapy. PI's do not require dose adjustment for advanced kidney impairment. 

Fusion inhibitors like Maraviroc and Integrase inhibitors like Raltegravir have no known kidney toxicity and do not need dose adjustment


Histology of HIVAN

Key features of HIVAN on light microscopy are proliferation of cells in the glomerular tuft, scarring of glomerular vessels (arrows) and cystic dilation of tubules (*).

Electron microscopy shows tubuloreticular inclusions in the endoplasmic reticulum of podocyte cells. It is important to note that a kidney biopsy is not always necessary. 


 If poor responses are obtained from ART and other treatments, a biopsy may be necessary to rule out other causes especially if salvage of remaining kidney function is considered a realistic goal of management. 


Treatment of HIVAN 

ART is the foundation of treatment of HIVAN. Initiating treatment quickly is vital and most important in improving prognosis. ART should NOT be delayed because of renal impairment. 

Angiotensin receptor blockers or angiotensin converting enzyme inhibitors are key tools in management of patients with HIVAN and an estimated creatinine clearance above 30 ml/min. 

Steroids have also been anecdotally used in managing patients especially if there is a strong interstitial inflammatory component to the renal biopsy findings. Care must be taken to eliminate or deal with other infections that may be worsened by steroid therapy before initiating steroids for HIVAN.

Issues in HIV patients on Dialysis

ART remains the conerstone of care and proper dosing and managing side effects is important. The dialysis prescriptions is no different from patients on dialysis without HIV. Malnutrition and increased risk of fractures should be anticipated and prevented by close attention to nutrition & bone metabolism.  Anemia due to ART as well as kidney failure will require erythropoietin and iron therapy. Hypertension is often less of an issue in these patients. 


Infections both routine and opportunistic, bacterial and non-bacterial occur more often in HIV patients on dialysis and need to be monitored, prevented and treated.

Kidney transplantation in patients with HIV

•Increasingly available in experienced centers. 

Two patients with HIV successfully transplanted and being followed carefully at KidneySolutions 

•Requires                                              –CD4 counts >200 for > 6 months          –Undetectable viral load for >6 months                                                 –No opportunistic infections in at least 6 months                                               –Stable ART regimen for at least 6 months

•Several drug-drug interactions between ART and transplant immunosuppresion to deal with requiring an experienced transplant team to manage.

•Rejection of the transplanted kidney  is often encountered despite presumed immunosuppressed state due to HIV.  Aggressive monitoring of both the kidney transplant and HIV infection is necessary.

•Long term graft and patient survival comparable to transplant in non HIV infected patients in experienced hands.