Clinicopathological profile of HIV kidney disease in South Africa – an evolving disease presentation or merely a genetic adaptation for survival?

 

AUTHORS: 

 

Glendah Kalunga¹, Raquel Duarte², Stewart Goetsch³, Pulane Mosiane⁴, Tobias Chirwa⁵, Martin Pollak⁶, Saraladevi Naicker¹

1. School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand
2. Molecular Biology, Faculty of Health Sciences, University of the Witwatersrand
3. Lancet Laboratory Pathology
4. Pathology, Faculty of Health Sciences, University of the Witwatersrand
5. Epidemiology, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand
6. Beth Israel Deaconess Medical Centre – Harvard University USA

 

INTRODUCTION:

Sub-Saharan Africa has the most serious HIV epidemic in the world. S.A. leads with prevalence of 17.9%. Chronic Kidney Disease (CKD) affects 15% of South Africans. The prevalence of HIV-CKD is 6%, with 50-60% considered classic HIVAN. This is what has been said for a long time. However, recent studies show downward trends in HIVAN occurrence. HIV people of African descent have an 18-50 fold ↑ risk for HIV-1-associated FSGS. Genetic susceptibility alone does not lead to HIVAN. Multiple hits in gene-gene/gene-environmental interactions are a requirement. We, therefore, asked ourselves the question; Is HIVAN a disappearing disease, a disease in evolution or merely a genetic adaptation for survival?

 

METHODOLOGY

Ongoing Prospective study. Participants recruited at 3 largest public hospitals in Johannesburg. Every patient presenting to the renal and HIV clinics is given opportunity to participate after informed consent. Patients with proteinuria are followed up for evidence of CKD. Descriptive analysis was conducted. Statistical tests conducted at 5% significance level. Analysis conducted using STATA version 13.

 

RESULTS

Table 1: Baseline Characteristics of Study Population

 

Characteristic	All patients (N=335)
Mean Age, yr (SD)	36.65 (10.05)
Mean BMI (SD)	25.59 (5.68)
Women, n (%)	186 (57.7)
HIV Status (Pos), n (%)	281 (83.8)
Mean Haemoglobin (SD)	11.38(2.39)
Mean Albumin (SD)	24.6 (8.16)
Mean serum creatinine, umol/l	230.4 (281.05)
HIV viral load < 40 copies/ml	9 (19.6)
HIV viral load > 40 copies/ml	37 (80.43)
Mean CD4 Count (SD)	326.5 (209.7)
UPCR > 3g	57 (45.6)
Microalbumin > 30	78 (42.16)

  

TABLE 2: Histological Profile

HISTOLOGICAL DIAGNOSIS		HIV Pos	HIV Neg
Focal segmental glomerulosclerosis	1o	9	3
	2o   →  HIVAN(collapsing FSGS +               microcystic dilatation)       →  Others	12
		6	2
	NOS	4
HIVICK(HIV Immune cpx kidney disease) / HIVICK-IgA subtype		15
IgA Nephropathy		6	5
MPGN		5	9
Membranous Glomerulopathy		5	7
Immune cpx GN		7	6
Diabetic nephropathy		4	2
ATN		7	3
Acute Post Infectious GN		1	3
Hypertensive Nephropathy		6	4
Chronic End stage kidney disease		1	0
Renal Amyloidosis		1(AA)	1(AL)
MCD		12	5
TOTAL		101	50

A total of 335 patients were recruited, 94.2% black. 281(84.5%) HIV positive with mean age of 36.52 (SD-10.05), 72.75% were HAART naïve, mean BMI of 25.6 (SD-5.7). 153 (52.04%) had CKD, 136 had kidney biopsies, 95 of whom were HIV positive. Some patients had more than one pathology on histology. Mean CD4 count was 326.5 Histopathological profile of the HIV positive patients shown in table 2;  FSGS – 30.7%, HIVAN – 12%, HIVICK – 14.6%, MCD -12%. 7 of the HIVANs were female, 5 of these had ESRD, 6 (50%) had CD4 counts less than 200 (15-929). 8 were on HAART for at least two years, although only two were virologically suppressed. One patient had features of both HIVAN and HIVICK on histology. All 12 were grossly proteinuric (2.25-29.6g/day). The HIVICK group did not exhibit any specific pattern, CD4 count ranged from 10 to 635; 3 (20%) had ESRD, proteinuria ranged from 0.03 to 6.12g/day). Viral loads and CD4 counts were found not to be predictive of HIVAN (p-values 0.11 and 0.53), although most patients did not have viral load results.

There was no association between the occurrence of HIVAN and the level of CD4 count, viral load, nephrotic range proteinuria and serum creatinine (p-values 0.53, 0.11, 0.3 and 0.42). There were statistically significant increases in the occurrence of FSGS, MCD and ATN in HIV patients in comparison with HIV negative group and vice versa for MPGN. MPGN was not the most common immune cpx GN in HIV+, in contrast to some studies. Statistically no differences noted in occurrence of membranous, IgA nephropathy, Immune complex disease and other glomerulonephritic lesions amongst the HIV positive and negative populations.

 

CONCLUSION: 

Our study describes the variety of renal pathology prospectively for HAART experienced and HAART naïve patients. We demonstrated that HIVAN cannot be differentiated from non-HIVAN kidney diseases without histology. The heterogeneity of HIV kidney diseases suggests a wide spectrum of injury. There appears to be a downward trend in the prevalence of HIVAN. This has been attributed to early initiation of HAART, modifying the immune status and enhancing immune complex GN (HIVICK). However, this does not appear to be the case in our cohort, as more than 50% of our HIVANs were on HAART for at least two years, and most of our HIVICKs were HAART naïve. This brings to the fore, dynamics of inadequate viral suppression, natural evolution of the HIV virus and the infection it causes or is this simply a genetic adaptation for survival (virus vs human)?

REFERENCES:

 

1. UNAIDS Global report 2013.
2. Stanifer JW, Jing B, Tolan S et al. The epidemiology of CKD in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Glob Health 2014.
3. Ross MJ, Klotman PE. Recent progress in HIV-Associated Nephropathy. JASN. 2002
4. Gerntholtz TE, Goetsch SJ, Katz I. HIV-related nephropathy: a South African Perspective. KI 2006 May 
5. Han TM, Naicker S, Ramdial PK. A cross-sectional study of HIV-seropositive patients with varying degrees of proteinuria in South Africa. KI 2006