Browsing by Author "Wearne, Nicola"

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    A comparison of clinical, biochemical, and histological characteristics as well as evaluation of outcomes of patient with mesangiovapillary glomerulonephritis (MCGN) in HIV positive and negative patients at a tertiary hospital in Cape Town, South Africa
    (2023) Sorathia, Shaheed Salim Gulamali; Wearne, Nicola; Jones Erika; Davidson, Bianca
    Background & Aim Mesangiocapillary glomerulonephritis (MCGN) is a common histological pattern of glomerular injury in developing countries. South Africa has the highest proportion of people living with HIV (PWH) and the co-existence of MCGN and HIV may affect kidney prognosis. The aim of this study was to compare the clinical and biochemical features between PWH and HIV-negative individuals with a diagnosis of MCGN and to review kidney function and survival. Materials and Methods A retrospective study was conducted in patients with a biopsy diagnosis of MCGN between January 2010 and December 2017. The following data were collected: age, sex, use of illicit drugs, date of initiation of antiretroviral therapy (ART), blood pressure, presence of oedema, need for kidney replacement therapy, HIV status, CD4 and viral load. Secondary causes were excluded. Kidney outcomes [(serum creatinine, estimated glomerular filtration rate (eGFR), urine protein creatinine ratio (uPCR)] were assessed at 6, 12 and 24 months post biopsy. The composite outcome was defined as a 40% decline in eGFR, progression to end stage kidney disease or death. Results: The study included 116 participants: 27 (23%) were PWH, 89 (77%) were HIV-negative. The median age was 33 years. There were more males in the HIV-negative group [63/89 (71%)]. Oedema was more common in HIV-negative patients [66/86 (77%), p=0.011]. Haemoglobin and albumin were lower in PWH [9.1g/dL vs 11.2 g/dL (p=0.053) and 20 g/L vs 27 g/L, (p=0.053), respectively]. Baseline creatinine, eGFR and uPCR were not different between the groups. However, at 6 and 12 months the creatinine was higher in PWH: 137 μmol/L compared to 97 μmol/L (p=0.028) and 125 μmol/L compared to 87 μmol/L(p=0.023), respectively. uPCR was higher in PWH at 6 and 12 months: 0.63 g/mmol vs 0.075 g/mmol, (p=0.002) and 0.28 g/mmol vs 0.028 g/mmol, (p=0.022), respectively. The composite endpoint was not different between the two groups in the first three years of follow-up.
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    Clinico-pathological characteristics and outcomes of nephrology adolescents and young adults in Cape Town: a single centre study
    (2022) Barday, Zibya; Davidson, Bianca; Wearne, Nicola; Jones, Erika; McCulloch, Mignon
    Background Adolescents and young adults [AYA] are important users of the nephrology health care services. Worldwide, there is a paucity of data on AYA kidney disease and outcomes. This study evaluates kidney outcomes, survival and challenges faced by AYA in a South African setting. Methods This 5-year retrospective study included AYA [aged 10-24] with chronic kidney disease, at a tertiary nephrology service in South Africa. Descriptive analysis characterised the aetiology of kidney disease. A comparative analysis of baseline characteristics, outcomes and social challenges were performed between patients attending a dedicated AYA clinic and those attending the standard adult clinics [non-AYA clinics]. Primary composite outcome assessed included doubling of creatinine, reduction of eGFR >40%, end-stage kidney disease and death. Logistic regression evaluated associations between relevant variables, death and lost to follow up [LTFU]. Results The total AYA cohort consisted of 292 patients, 111 (38.0%) attended the AYA clinic and 181 (62.0%) the non-AYA clinics. The main aetiologies of disease were glomerular 212 (72.6%), congenital anomalies of the urinary tract 31 (10.6%), and hereditary conditions 24 (8.2%). There was a significantly lower mortality (p=0.007) and reduction in LTFU (p=0.012) in the cohort attending the AYA clinic. A statistically significant composite outcome (p=0.018), with improved kidney survival was found in the AYA clinic group. High proportions of nonadherence (33.9%) and substance use (25.0%) was demonstrated in both cohorts. Conclusion This study adds to the dearth of literature on AYA kidney disease. A dedicated nephrology AYA clinic is shown to have lower mortality, less LTFU and improved kidney outcomes, which is essential in a resource-limited setting where access to kidney replacement therapy is restricted.
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    Diagnostic performance of glomerular PLA2R and THSD7A antibodies in biopsy confirmed primary membranous nephropathy in South Africans
    (2021-01-07) Lwezaula, Bingileki F; Ameh, Oluwatoyin I; Ekrikpo, Udeme E; Botha, Francois C; Okpechi-Samuel, Ugochi S; Wearne, Nicola; Ronco, Pierre; Bello, Aminu K; Okpechi, Ikechi G
    Background: Serum and tissue-based tests using phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain containing 7A (THSD7A) are established immune biomarkers for the diagnosis of primary membranous nephropathy (PMN). This study assessed the diagnostic performance of these biomarkers in the diagnosis of PMN in South Africans. Methods This was a cross-sectional analysis from a single centre in Cape Town, South Africa. Relevant biodata was collected from all patients. Histology, including slides for PLA2R and THSD7A were processed and assessed by typical microscopic and immunohistochemical features. Biopsy tissues of patients with membranous lupus nephritis (LN-V) and diabetic nephropathy (DN) were used as controls. The diagnostic accuracy for diagnosis of PMN using positive PLA2R and THSD7A were evaluated. Results Of the 88 patients included, 41 had PMN with a mean age of 44.5 ± 17.5 years and 61.0% were female. Histologically, PLA2R and THSD7A were only positive in the PMN group (51.2% and 4.9%, respectively) but negative in both control groups. The sensitivity of PLA2R and THSD7A for identifying PMN was 51.2% and 4.9%, respectively. The sensitivity of both tests together was 53.7% while the specificity and positive predictive values (PPV) for any of the tests (alone or in combination) was 100%. There was no difference in the sensitivity and specificity when using PLA2R alone compared to combining the two tests (p=0.32). Conclusion Glomerular staining of PLA2R and THSD7A could have potential diagnostic values in South Africans. This has implications on how immunotherapies can be initiated and used in these settings.
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    Histological evidence and clinical Correlations of renal TB-IRIS in HIV-positive patients and outcomes
    (2018) Kahn, Thania; Wearne, Nicola
    Background Tuberculosis immune reconstitution inflammatory syndrome [TBCIRIS] is a well described clinical entity in HIV-infected patients that can affect multiple organs. There is however a paucity of information regarding renal involvement. This study aimed to illustrate the clinical, biochemical and histopathological features of HIV patients with suspected renal TBCIRIS, and to assess the mortality and renal outcomes of these patients. Methods The study was an observational, retrospective review of two established HIV positive renal biopsy registries [Groote Schuur Hospital and Livingstone Hospital Port Elizabeth, Eastern Cape].Renal biopsies were reviewed for the presence of granulomatous interstitial nephritis [GIN]. Patients’ folders and laboratory records were reviewed for evidence of tuberculosis [TB] and TBCIRIS. They were also reviewed for other causes of GIN i.e. drugs, fungal infection, sarcoidosis and infection. The study was approved by the UCT research ethics committee. The data was then analysed comparing 3 groups: [TB: no IRIS] (all TB cases with no features of IRIS), [TB + IRIS] (all cases with features of TBCIRIS) and [Other] (other causes of GIN). Results 68 HIV-positive renal biopsies were identified with GIN. The mean age was 37.5±9.1 years. There were 33 males (48.5%); 61 (89.7%) were of African black ethnicity, and there were no Caucasians in the study. 29 patients (43%) were noted to be on other medications known to cause GIN. The mean time from ART initiation to biopsy was 12 weeks, with the shorter average time being in the [TB + IRIS] group (6 weeks). The mean CD4 at biopsy was 105cells/µL, with the lowest CD4 seen in the in the [TB + IRIS] group (81cells/µL) (PC value 0.0175). The granulomas in the [TB + IRIS] group were noted to be more well-formed, with the highest number of poorly formed granulomas found in the [TB: no IRIS] group (25%) Sixteen (25%) of subjects had died within 2 years of their biopsy, with the majority of deaths occurring in the [TB : no IRIS] group (12/48, 44%), (PCvalue!0.01). Conclusion This study is the largest series of renal TBCIRIS that adds to the very limited case reports in the literature. There is a clinical entity of TB renal CIRIS that is associated with GIN on renal biopsy. Significant findings were those of a shorter time from ART initiation to biopsy in the [TB + IRIS] group, a lower CD4 count at biopsy and nadir in the [TB + IRIS] group with more well-formed granulomas. The majority of deaths within 2 years were noted in the [TB: no IRIS] group. This entity seems to be in keeping with other TBC IRIS descriptions previously published.
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    Impact of socio-economic factors and Health Related Quality of Life on patients on renal dialysis in Cape Town
    (2020) Welgemoed, Waldo; Wearne, Nicola; Davidson, Bianca
    Background: South Africa [SA] has a growing burden of chronic kidney disease [CKD], with limited health resources. Cape Town offers a PD-First policy due to both limitations on haemodialysis slots and cost saving measures. This study aimed to compare health related quality of life [HRQOL] between haemodialysis [HD] and peritoneal dialysis [PD], given the lack of autonomy in modality choice and socioeconomic challenges our patients face. Methods: This cross-sectional study was performed at Groote Schuur Hospital between July 2015 and December 2016. Demographic, socio-economic variables and perception of safety were collected. HRQOL was assessed using the Kidney Disease Quality of Life-Short Form [KDQOL-SFTM] version 1.3. All data was compared between the two dialysis modalities. Results: 77 HD patients and 33 PD patients were included in the study (Total n=110). There were no significant differences in demographics. The median age was 42.5 years [IQR: 32.4-48.6] and 57.3% were female. HD patients had less pain [p=0.036], better emotional well-being [p=0.020] and better energy/fatigue score [p=0.015]. Both cohorts experienced impairment in physical health, with PD having significant limitation [p=0.05]. The only significant symptoms in the renal domain was that PD experienced more shortness of breath [p=0.0001]. Overall, patients in both groups had very poor socio-economic circumstances. Safety was a major concern with the majority reporting feeling unsafe in their homes. Conclusions: The patients in our dialysis service have very challenging social circumstances with high rates of poverty and profound safety concerns. Patients on PD scored worse in 4 HRQOL domains, possibly due to a lack of autonomy in dialysis modality choice and less frequent contact with dialysis staff to provide encouragement and support. Additional psychological and social support needs to be instituted to help improve our patient's wellbeing on PD.
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    Kidney tissue characterization using magnetic resonance in HIV infected individuals undergoing kidney biopsy
    (2024) Banda, Tayanjana; Rayner, Brian; Wearne, Nicola; Ntusi, Ntobeko
    BACKGROUND: Kidney disease is a common complication of human immunodeficiency virus (HIV) infection. Kidney biopsy is the gold standard for assessing causation, but being invasive, it carries increased risk in advanced chronic kidney disease (CKD). Magnetic resonance imaging (MRI) is noninvasive and may serve as an alternative to kidney biopsy in a subset of patients. OBJECTIVES: The primary aim of this study was to compare the kidney biopsy Sethi chronicity score and MRI findings. METHODS: This was a prospective pilot study, conducted at Groote Schuur Hospital, Cape Town and the Cape Universities Body Imaging Centre (CUBIC). People with HIV (PWH) >18 years with a clinical indication for kidney biopsy were included. Demographics and other clinical data were documented. Uncontrasted MRI scans were performed between 1-7 days prior to kidney biopsy that included diffusion tensor imaging (DTI), and proton (H1) spectroscopy. The kidney biopsy Sethi chronicity score was compared to MRI-DTI using linear regression modeling as well as with H1 spectroscopy. RESULTS: Sixteen participants were included in the study. Thirty-one percent were female, 47% hypertensive, 6% diabetic, 44% had current tuberculosis, and 56 % were receiving antiretroviral therapy {ART). The most common histology observed on kidney biopsy were granulomatous interstitial nephritis (31%}, hypertensive changes (31%) and HIV associated nephropathy (HIVAN) (25%). Mixed pathology was observed in 25% of participants. There was significant negative correlation with Sethi chronicity score and MRI-DTI findings. Spectroscopy showed an element of cell degradation and inflammation in all participants with highest lipid peaks in participants with HIVAN, and pauci-immune crescentic glomeru!onephritis. CONCLUSION: In this small pilot study Sethi chronicity scores negatively correlated with MRI-DTI findings suggesting that this may potentially be a useful tool to assess chronicity. Further research ls required to corroborate these findings and include BOLD sequence and Tl and T2 parametric mapping.
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    Patient outcomes in a PD First Program in Cape Town, South Africa
    (2017) Davidson, Bianca; Wearne, Nicola
    Background: South Africa [SA] currently performs the most peritoneal dialysis [PD] in Africa. Yet, outcome data is limited. With the collision of epidemics of communicable and non-communicable diseases in Africa the need for chronic dialysis is escalating. PD remains a life-saving modality especially as haemodialysis is limited in the state sector. Methods: We retrospectively analysed all patients undergoing PD at Groote Schuur Hospital from January 2008 until June 2014 and thereafter prospectively until June 2015. Variables included demographics, adequacy, modality, fluid, cardiovascular risk and diabetes. The influences of these variables on peritonitis rate, technique and patient survival were assessed. Results: 230 patients were initiated on PD, 31 were excluded as they were on PD for < 90 days. The mean age was 39.7 +/- 10.4 years [SD], 49.8% were male and 63.8% were mixed ancestry. 9.8 % were diabetic at dialysis initiation. The average length of time on PD was 17 months (IQR 8 - 32). The peritonitis rate was 0.87 events per patient years. One, 2 and 5 year patient and technique survival was 94.4%, 84.3% and 60.2% and 82.5%, 69.0% and 37.4% respectively. Fluid overload (p=0.019) and low haemoglobin (p=0.001) were independent risk factors for poor survival. African race (HR 1.97, 95% CI (1.16 - 3.37) and fluid overload (p= 0.002) were both predictors of technique failure. Conclusions: In our PD-First programme the results are encouraging, despite lack of home visits due to safety, resource limitations and a high disease burden. Technique failure in African race needs further evaluation. Peritoneal dialysis remains a viable, life-saving alternative in an African setting.
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    A retrospective review of Granulomatous Interstitial Nephritis (GIN) amongst HIV-infected patients at Groote Schuur Hospital, Cape Town
    (2014) Nel, Debbie; Wearne, Nicola
    Introduction: High numbers of granulomata have been identified on kidney biopsy at Groote Schuur Hospital in HIV positive patients. In the literature granulomatous interstitial nephritis (GIN) is most commonly attributed to sarcoid and drug reactions and occurs in 0.5- 1.37% of kidney biopsies. Current data is only from developed countries and rarely in HIV positive individuals. As our yield of GIN appeared high we retrospectively reviewed the established HIV database of kidney biopsies to establish the likely causes of this histological finding in our HIV positive population. An extensive literature review was also performed with the intention of developing a diagnostic, and therapeutic, algorithm applicable to GIN in a South African setting. Subjects and Methods: A database of 370 HIV positive kidney biopsies dating from January 2005 was retrospectively reviewed. All patients with GIN on kidney biopsy were analysed. Medication history, creatinine, urine protein/creatinine ratio, CD4 count and serological evidence of vasculitis were recorded. A radiological evaluation and search for positive TB cultures was performed. Patients were divided according to the likely aetiology of GIN, ranging from least to most likely TB-GIN, together with the likelihood of a druginduced or ascending infection-related aetiology. Mortality data was obtained from reviewing the Clinicom system and patient records. Ethics was granted from the UCT ethics committee. Results: 45 patients (12.2%) had evidence of (GIN). 26 (57.8%) were female. Median age was 33 years (IQR 29-37). TB-GIN was likely in 62.2% of patients .Median CD4 was 126 cells/mm3 (IQR 54-237). There were 6 cases of possible paradoxical TB IRIS identified. [median CD4 count of 74 cells/mm3 (IQR 36-170)]. 49% of patients were on a drug implicated in GIN, with 11% on >1 drug [The most common drug being cotrimoxazole]. 6 patients had evidence of ascending infection. No patients had vasculitis.14/45 (31%) patients died on follow up with a median time to death of 119 days (IQR 30-444 days). Interpretation: GIN is common in our HIV population. TB is the most likely cause however other aetiologies require consideration, especially drugs. TB IRIS should be considered if cART has been recently initiated and the CD4 count is low. A proposed diagnostic algorithm was developed as part of this study, together with treatment guidelines. Further research is needed to evaluate the utility of these in a clinical setting.
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    The 5 year outcomes of patients receiving haemodialysis versus peritoneal dialysis at Groote Schuur Hospital, Cape Town, South Africa
    (2018) Crombie, Kenneth; Wearne, Nicola
    Background: Despite the rising global prevalence of chronic kidney disease, dialysis remains restricted in South Africa and acceptance onto many renal replacement programs is limited to those suitable for transplantation. Few studies exist comparing survival outcomes of peritoneal dialysis [PD] and haemodialysis [HD] patients from developing countries. In addition, data of those switching to HD are conflicting. Methods: This retrospective cohort study compares survival outcomes of patients receiving HD or PD at Groote Schuur Hospital, South Africa, from 2010- 2015. Results: 174 patients were assigned to HD and 189 to PD, of which 42 switched to HD. The majority (68.31%) of patients were under 45 years. More black Africans received HD. The most common causes of death were infection (26%) and fluid overload (19%). Having removed those PD patients for whom modality switch was denied due to contraindications to transplantation, survival probability at 1-, 2- and 5- years for HD versus PD was 98.68% (CI: 94.84-99.67), 96.95 (CI: 91.98-98.86) and 83.52% (CI: 71.75-90.70) versus 96.73% (95% CI: 92.32- 98.63), 89.95 (95% CI: 83.17- 94.1) and 76.69 (95% CI: 60.97- 86.73) respectively. (p= 0.145) The survival probability of those patients who switched from PD to HD, for the same intervals was 100%, 97.37% (95% CI: 82.75-99.63) and 97.37 % (95% CI: 82.75-99.63). (p=0.001) Conclusion: In this setting, PD is not inferior to HD and those patients switching from PD to HD have the best survival outcomes. Therefore, the current local PD first policy is justified, although interventions should be aimed at improving outcomes.
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    The effects of add-on corticosteroids on renal outcomes in patients with biopsy proven HIV associated nephropathy: a single centre study from South Africa
    (BioMed Central, 2019-02-06) Wearne, Nicola; Swanepoel, Charles R; Duffield, Maureen S; Davidson, Bianca J; Manning, Kathryn; Tiffin, Nicki; Boulle, Andrew; Rayner, Brian L; Naidu, Priyanka; Okpechi, Ikechi G
    Background The aim of this study was to assess, the efficacy and safety of add-on corticosteroids to antiretroviral therapy [ART] in patients with biopsy proven HIV associated nephropathy. Methods All included patients had histological evidence of either collapsing or non-collapsing focal segmental glomerulosclerosis (FSGS) or podocyte and/or parietal cell hypertrophy or hyperplasia. All patients had evidence of tubulointerstitial inflammation with microcysts. Patients were randomized to ART with the addition of 1 mg/kg of corticosteroids [ART+C] or remained in the group [ART Alone] and followed for 2 years. A repeat biopsy was performed at 6 months. Results Twenty-one patients were randomized to [ART+C] and 17 to [ART Alone]. The baseline estimated glomerular filtration rate (eGFR) was significantly lower in the [ART+C] vs. [ART Alone] group [35mls/min/1.73m2 vs. 47 mls/min/1.73m2, p = 0.015]. The [ART+C] cohort had a statistically significant improvement in median (eGFR) from baseline to last follow up compared with [ART Alone] i.e. [Δ = 25mls/min (IQR: 15;51) vs 9 mls/min (IQR: 0–24), p = 0.008]. There were no statistically significant differences between the groups when proteinuria and histology were analyzed. There were 8 deaths during the trial period, 7 from [ART+C] (Log rank p = 0.071). Conclusions In the [ART+C] cohort there was a significant improvement in eGFR over 2-years with increased mortality. Routine corticosteroid use cannot currently be recommended. Further investigation to define which subgroup of this cohort would safely benefit from the positive effects is required. Trial registration ISRCTN study ID ( 56112439 ] was retrospectively registered on the 5 September 2018.