Leadership and early strategic response to the SARS-CoV-2 pandemic at a COVID-19 designated hospital in South Africa.

While many countries are preparing to face the COVID-19 pandemic, the reported cases in Africa remain low. With a high burden of both communicable and non-communicable disease and a resource-constrained public healthcare system, sub-Saharan Africa is preparing for the coming crisis as best it can. We describe our early response as a designated COVID-19 provincial hospital in Cape Town, South Africa (SA).While the first cases reported were related to international travel, at the time of writing there was evidence of early community spread. The SAgovernment announced a countrywide lockdown from midnight 26 March 2020 to midnight 30 April 2020 to stem the pandemic and save lives. However, many questions remain on how the COVID-19 threat will unfold in SA, given the significant informal sector overcrowding and poverty in our communities. There is no doubt that leadership and teamwork at all levels is critical in influencing outcomes.

Leadership and early strategic response to the SARS-CoV-2 pandemic at a COVID-19 designated hospital in South Africa

While many countries are preparing to face the COVID-19 pandemic, the reported cases in Africa remain low. With a high burden of both communicable and non-communicable disease and a resource-constrained public healthcare system, sub-Saharan Africa is preparing for the coming crisis as best it can. We describe our early response as a designated COVID-19 provincial hospital in Cape Town, South Africa (SA).While the first cases reported were related to international travel, at the time of writing there was evidence of early community spread. The SA government announced a countrywide lockdown from midnight 26 March 2020 to midnight 30 April 2020 to stem the pandemic and save lives. However, many questions remain on how the COVID-19 threat will unfold in SA, given the significant informal sector overcrowding and poverty in our communities. There is no doubt that leadership and teamwork at all levels is critical in influencing outcomes

The state of kidney transplantation in South Africa.

BACKGROUND: Kidney transplantation has been performed in South Africa (SA) since 1966. Transplants were initially limited to public hospitals, and the entry of the private sector heralded a new era in organ transplantation. OBJECTIVES: To document kidney transplantation in SA and compare numbers, rates, trends and sources of kidneys transplanted in the public and private sectors in SA over 25 years. METHODS: National kidney transplant data collected between 1991 and 2015 by the Organ Donor Foundation of South Africa were analysed. The total number of kidneys transplanted in the country was counted and rates were calculated. The numbers and rates in the private and public sectors were compared. The source of donor kidneys and sites where transplants were performed were documented. RESULTS: Over the 25-year period under review, 7 191 kidney transplants were performed in SA. The overall kidney transplant rate was 6.4 per million population (pmp), averaging 4.8 pmp in the public sector and 15.2 pmp in the private sector; 58.3% of the donor kidneys were derived from deceased donors. Cape Town and Johannesburg hospitals performed 75% of the country's kidney transplants. CONCLUSIONS: The overall transplant rate in SA is declining, especially in the public sector. Most kidney transplants in the country were performed in the public sector, and deceased-donor transplants predominated. Discrepancies exist in the allocation of kidneys. Recommendations are made on how the situation may be improved.

The clinical relevance of repeat renal biopsies in the management of lupus nephritis: a South African experience.

Purpose Clinically, repeat renal biopsies (RRBs) have been performed in lupus nephritis to identify changes in class, plan treatment and assist in prognostication. We set out to compare the histopathological features and outcomes of disease flare and protocol biopsy patients. Methods A retrospective descriptive study was conducted on repeat biopsies performed between January 1984 and December 2015 in lupus nephritis patients. Disease flares and protocol biopsies were compared. Results Of 614 systemic lupus erythematosus (SLE) renal biopsies, 127 (20.7%) RRBs were identified. Disease flare patients accounted for 96 (75.6%) and protocol biopsies for 31 (24.4%) of RRBs. Seventy (72.9%) disease flare patients retained their original class on repeat biopsy. When categorised as proliferative and non-proliferative histology, 83 (87.4%) of the disease flare biopsy patients remained histologically unchanged. Treatment remained unchanged in 57 (60.0%) patients following RRBs for disease flares. Response to immunosuppression in disease flare patients was poorer. Non-response was associated with increased chronicity index (OR = 1.33; 95% CI 1.01-1.76; p = 0.045). Thirty-three (36.3%) disease flare patients developed end-stage kidney disease (ESKD) in one year as compared to one (3.6%) protocol biopsy patient ( p = 0.003). ESKD in disease flare patients was associated with non-response to treatment (OR = 24.6; 95% CI 2.7-219.3; p = 0.004) on multivariate analysis. One-year mortality was 30.0% in the disease flare patients and 3.5% in protocol biopsy patients ( p = 0.018). Conclusion Repeat biopsies in disease flare patients infrequently led to histological class changes, failed to lead to change of treatment in the majority of patients, and were associated with poorer outcomes.

Lupus nephritis in the Western Cape, a high prevalence area: an experience over three decades.

Background Systemic lupus erythematosus is a multisystem disease with serious complications, including lupus nephritis. Systemic lupus erythematosus is prevalent in the Western Cape, predominantly affecting women in the prime of their lives. Renal biopsy is an important tool for the management of the lupus patient with kidney disease, guiding treatment and assessing prognosis. Aims The aim of this study was to ascertain if there has been a change in the spectrum of renal pathology, patient characteristics and long-term outcomes in patients with lupus nephritis in our region over three decades. Methods We reviewed 315 records of systemic lupus erythematosus patients with suspected renal disease who underwent renal biopsy in the Renal Unit at Tygerberg Hospital over three decades between January 1983 and December 2012. Results Lupus nephritis consistently affected young women. Class IV lupus nephritis remained the most common pattern throughout the three decades. The overall five-year survival for this cohort was 67% (95% confidence interval (CI), 60-72%). Conclusion Class IV lupus nephritis remained the most frequent class in our cohort of patients with the poorest survival rates compared to other classes. The prognosis of lupus nephritis in our region is considerably worse than that reported elsewhere in the world.

Calcific uraemic arteriolopathy (calciphylaxis) in patients on renal replacement therapy.

BACKGROUND: Calcific uraemic arteriolopathy (calciphylaxis) is an unusual and potentially fatal condition characterised by small-vessel calcification and ischaemic skin necrosis. It mainly affects patients with end-stage renal disease (ESRD) on haemodialysis, but may rarely occur in the absence of ESRD in conditions such as primary hyperparathyroidism, malignancy, alcoholic liver disease and connective tissue disease. METHODS: We reviewed the records of all patients diagnosed with calciphylaxis while on renal replacement therapy at Tygerberg Hospital, Cape Town, South Africa, between 1990 and 2014, to describe its presentation, course and final outcome. RESULTS: Nineteen patients developed calciphylaxis over this period. Their median age was 34 years and 13 (68.4%) were female. Fifteen (78.9%) had received a kidney transplant. All patients had painful skin lesions that rapidly progressed to infarction. Small-vessel calcification was seen on skin biopsy in 13 patients. Twelve patients had hyperparathyroidism. Several of the transplanted patients had been treated for graft rejection in the year preceding the diagnosis. Treatment consisted of good wound care and efforts to normalise serum calcium and phosphate levels. Five patients received an urgent parathyroidectomy. The outcome was fatal in 17 patients, with sepsis being the main cause of death. CONCLUSIONS: In our patients, calciphylaxis carried a worse prognosis than previously reported internationally. It should always be considered in the differential diagnosis of painful skin lesions in the dialysis or transplant patient.

Calcific uraemic arteriolopathy (calciphylaxis) in patients on renal replacement therapy

Background. Calcific uraemic arteriolopathy (calciphylaxis) is an unusual and potentially fatal condition characterised by small-vessel calcification and ischaemic skin necrosis. It mainly affects patients with end-stage renal disease (ESRD) on haemodialysis, but may rarely occur in the absence of ESRD in conditions such as primary hyperparathyroidism, malignancy, alcoholic liver disease and connective tissue disease.Methods. We reviewed the records of all patients diagnosed with calciphylaxis while on renal replacement therapy at Tygerberg Hospital, Cape Town, South Africa, between 1990 and 2014, to describe its presentation, course and final outcome.Results. Nineteen patients developed calciphylaxis over this period. Their median age was 34 years and 13 (68.4%) were female. Fifteen (78.9%) had received a kidney transplant. All patients had painful skin lesions that rapidly progressed to infarction. Small-vessel calcification was seen on skin biopsy in 13 patients. Twelve patients had hyperparathyroidism. Several of the transplanted patients had been treated for graft rejection in the year preceding the diagnosis. Treatment consisted of good wound care and efforts to normalise serum calcium and phosphate levels. Five patients received an urgent parathyroidectomy. The outcome was fatal in 17 patients, with sepsis being the main cause of death.Conclusions. In our patients, calciphylaxis carried a worse prognosis than previously reported internationally. It should always be considered in the differential diagnosis of painful skin lesions in the dialysis or transplant patient

Important causes of chronic kidney disease in South Africa.

In hypertensive patients without chronic kidney disease (CKD) the goal is to keep blood pressure (BP) at ≤140/90 mmHg. When CKD ispresent, especially where there is proteinuria of ≥0.5 g/day, the goal is a BP of ≤130/80 mmHg. Lifestyle measures are mandatory, especiallylimitation of salt intake, ingestion of adequate quantities of potassium, and weight control. Patients with stages 4 - 5 CKD must be carefullymonitored for hyperkalaemia and deteriorating kidney function if angiotensin-converting enzyme (ACE) inhibitors or angiotensin IIreceptor blockers (ARBs) are used, especially in patients >60 years of age with diabetes or atherosclerosis. BP should be regularly monitoredand, where possible, home BP-measuring devices are recommended for optimal control.Guidelines on the use of antidiabetic agents in CKD are presented, with the warning that metformin is contraindicated in patients withstages 4 - 5 CKD.There is a wide clinical spectrum of renal disease in the course of HIV infection, including acute kidney injury, electrolyte and acid-basedisturbances, HIV-associated glomerular disease, acute-on-chronic renal disease and side-effects related to the treatment of HIV.

Acute tubulointerstitial nephritis related to antituberculous drug therapy.

BACKGROUND: Acute tubulointerstitial nephritis (ATIN) as a complication of antituberculous therapy has been most commonly reported due to rifampicin therapy. This reaction typically occurs following re-exposure to the drug. This study undertook to investigate the clinicopathological features of ATIN related to antituberculous therapy. METHODS: We performed a retrospective study of all adult patients with a biopsy-proven diagnosis of ATIN on chemotherapy for tuberculosis. The patients presented with acute renal failure at our institution during 1995 - 2007. The demographic, clinical, biochemical and histopathological features were studied. The patient outcome and management were analyzed. RESULTS: 41 patients had histologically proven ATIN. 23 (56%) were female. The mean age at presentation was 42 years. The most common regimen included rifampicin used intermittently to treat pulmonary tuberculosis. The average duration of antituberculosis therapy was 19 days before presentation and the duration of the acute illness averaged 5 days. The most common clinical manifestation included gastro-intestinal symptoms occurring in 35 (85%) patients with associated hepatitis biochemically in 20 (53%) patients. No skin rashes were observed and eosinophilia was only present in two patients. Hematuria was observed universally without any significant proteinuria. Anemia was present in 37 (90%) patients, with associated thrombocytopenia in 15 (37%). Rifampicin was discontinued in 37 (90%) cases. Nine (22%) patients required dialysis. One patient failed to recover renal function and 4 (10%) patients died. Mortality was related to overwhelming tuberculosis infection. The main factor predicting the need for dialysis was duration of oliguria. CONCLUSION: ATIN is a rare, but serious complication of repeat antituberculous therapy mainly due to re-exposure to rifampicin. Although the renal prognosis is generally good the disease does carry significant morbidity and mortality risks. A high index of suspicion is needed in re-treatment patients. A suggested screening test is for microhematuria with urine dipstix.

Acute renal failure in the medical ICU still predictive of high mortality.

BACKGROUND: We aimed to determine the outcome and certain predictors of outcome for acute renal failure (ARF) in the medical intensive care unit (ICU) at Tygerberg Hospital. METHOD: We conducted a retrospective, single-centre cohort study over 12 months comprising all patients admitted to the medical ICU with all causes of renal failure or who developed renal failure following admission to the ICU. RESULTS: Of 198 medical patients admitted to the ICU, ARF occurred in 46 (23.2%). The leading cause of ARF was acute tubular necrosis. The ICU mortality for ARF patients was 47.8%, compared with 17.5% in ICU patients without ARF. Acute haemodialysis was performed in only 17.3% of the 46 ARF patients. Using Cox proportional hazard regression, we found that mean duration of stay (p<0.001), acute physiology and chronic health evaluation II (Apache II) score (p<0.001), mechanical ventilation (p<0.01), dialysis (p<0.04) and multi-organ failure (p<0.05) affected survival time. CONCLUSIONS: We found that ARF is still associated with a high mortality rate and longer duration of stay, higher Apache II score, and need for mechanical ventilation; dialysis and presence of multi-organ failure were indicators of a higher mortality rate.

The dangers of rationing dialysis treatment: the dilemma facing a developing country.

The increasing burden of chronic kidney disease places enormous strains on resources of all countries, but especially of those with emerging economies. Few developing countries are able to afford dialysis programs and those that do ration this scarce resource. In South Africa, rationing has been practiced since the introduction of dialysis. Our renal unit carefully screened patients with end-stage kidney disease (ESKD) based on certain medical and socioeconomic criteria. The outcome of these decisions taken by the Assessment Committee is reviewed in this study. Details of the 2442 patients with ESKD assessed between 1988 and 2003 for the renal replacement program were captured. Using univariate and multivariate analysis, the odds of being accepted for treatment based on several variables were determined. The majority (52.7%) of patients with ESKD were not offered renal replacement therapy in the period of study. The number of kidney transplants progressively decreased, as did the number of patients accepted. The patients mostly likely to be accepted for renal replacement therapy were aged 20-40 years, white, employed, married, non-diabetic, and lived in proximity to a dialysis center. Almost 60% of patients were denied renal replacement treatment because of social factors related to poverty. In a developing country, where rationing of treatment is unavoidable, it is difficult to ensure equity of treatment and certain groups are advantaged over others. In our experience, socioeconomic factors influenced decision to accept patients more profoundly than medical ones.

Kaposi's sarcoma in kidney transplant recipients: a 23-year experience.

BACKGROUND: Kaposi's sarcoma (KS) is a relatively common malignancy after kidney transplantation, accounting for up to 80% of all malignancies in developing countries. AIM: To assess the frequency of KS in renal transplant recipients, and determine the impact of demographic factors, immunosuppression and treatment options. DESIGN: Retrospective study in a single centre in South Africa. METHODS: Charts and pathology reports of 542 recipients of 623 kidney allografts treated at our institution between 1976 and 1999 were reviewed. RESULTS: After a mean follow-up of 6.4 years, 21 (3.9%) recipients had KS, representing 47.7% of all post-transplant malignancies. KS accounted for more post-transplant cancers in non-White than White patients (79.1% vs. 11.7%, p < 0.001). KS was equally common in males and females, and was not more frequent under cyclosporine. Skin involvement was universal; visceral disease occurred in six patients (28.6%). Sixteen (94.1%) patients with limited skin disease and two (100%) with superficial nodal disease responded to withdrawal or reduction of immunosuppression. Renal function was preserved when immunosuppression was reduced instead of withdrawn (p = 0.02). Patients with vital organ involvement succumbed rapidly to KS. Post-mortem examination revealed more extensive disease than was suspected clinically. DISCUSSION: Ethnic differences exist in the frequency of KS in patients residing in the same geographical area. Since withdrawal results in graft loss, reducing immunosuppression should be first-line treatment for patients with disease limited to skin, and possibly for disease of the superficial lymph nodes. The malignant behaviour of KS, and extent of pathological involvement, cast doubt on the idea that KS is a hyperplasia rather than a true malignancy.

Nutritional status of renal transplant patients.

OBJECTIVE: To assess the effect of renal transplantation on the nutritional status of patients. DESIGN: Prospective descriptive study. SETTING: Renal Transplant Clinic at Tygerberg Hospital, Western Cape. SUBJECTS: Fifty-eight renal transplant patients from Tygerberg Hospital were enrolled in the study. The sample was divided into two groups of 29 patients each: group 1, less than 28 months post-transplant; and group 2, more than 28 months post-transplant. OUTCOME MEASURES: Nutritional status assessment comprised biochemical evaluation, a dietary history, anthropometric measurements and a clinical examination. RESULTS: Serum vitamin B6 levels were below normal in 56% of patients from group 1 and 59% from group 2. Vitamin B6 intake, however, was insufficient in only 14% of patients from group 1 and 10% from group 2. Serum vitamin C levels were below normal in 7% of patients from group 1 and 24% from group 2, while vitamin C intake was insufficient in 21% and 14% of patients from groups 1 and 2 respectively. Serum magnesium levels were below normal in 55% of patients from group 1, and in 28% from group 2. Serum albumin and cholesterol levels increased significantly during the post-transplant period in the total sample (P = 0.0001). There was also a significant increase in body mass index (P = 0.0001) during the post-transplant period. CONCLUSIONS: Several nutritional abnormalities were observed, which primarily reflect the side-effects of immunosuppressive therapy. The causes, consequences and treatment of the vitamin B6 and vitamin C deficiencies in renal transplant recipients need further investigation.

Protein-energy malnutrition as a risk factor for increased morbidity in long-term hemodialysis patients.

This prospective nonintervention single-center study was undertaken to investigate the role of protein-energy malnutrition (PEM) as a risk factor for morbidity in patients on long-term hemodialysis. Thirty-seven patients from the renal unit of Tygerberg Hospital, Tygerberg, South Africa, were studied for a mean period of 26 months. Morbidity was the main outcome and was defined as the number of hospitalizations and days of hospitalization per patient per year. Investigations included 4-monthly determinations of interdialytic protein catabolic rate (PCR), dietary intake of protein and energy, blood levels of albumin and urea, lymphocyte count, adequacy of dialysis (Kt/V), body weight, intradialytic weight loss, fat mass (FM), fat-free mass (FFM), body mass index (BMI), and bone-free arm muscle area (BF-AMA). A PEM composite score was derived from postdialysis serum albumin, BF-AMA, FM, FFM, and BMI. All-cause morbidity as defined by number of hospitalizations (see text for other definitions of morbidity) showed a significant correlation with the mean and baseline PEM score (P <.01), and a negative correlation with predialysis and postdialysis serum albumin (P <.05) and age (P <.05). There was no significant relationship with PCR, percentage intradialytic weight loss, Kt/V, reuse of dialyzer, period on maintenance hemodialysis, sex, race, and type of dialyzer membrane. When "only infection-related" morbidity was considered, the factors that showed a significant correlation were the mean (P <. 001) and baseline PEM score (P <.01), and percentage intradialytic weight loss (P <.01). There was no significant deterioration in the nutritional status of patients followed up for at least 24 months. It is concluded that infection-related morbidity was associated most strongly with the PEM score and the percentage intradialytic weight loss. The results suggest that PEM is one of the important contributing factors to morbidity, possibly via an effect on the immune system and infection.

Detection and subtyping of human herpesvirus-8 in renal transplant patients before and after remission of Kaposi's sarcoma.

BACKGROUND: Kaposi's sarcoma (KS) is a complication of renal transplantation. If the human herpesvirus-8 (HHV-8) causes KS, the virus should be present in all KS lesions and be drastically reduced or cleared from involved tissue on remission of the KS. METHODS: Fourteen renal transplant patients with cutaneous KS, including autopsy material from two cases, were investigated for the presence of HHV-8. A second skin biopsy was taken from 11 survivors, after remission of KS, from normal skin in the same anatomical region as the first biopsy. Remission was induced by reduction or cessation of immunosuppression. A peripheral blood sample was collected simultaneously with the repeat biopsy. A nested polymerase chain reaction assay was used to detect HHV-8 DNA in the biopsy tissue and peripheral blood mononuclear cells followed by direct sequencing of polymerase chain reaction product to detect any nucleotide changes. RESULTS: HHV-8 DNA was detected in all the cutaneous KS and all the visceral KS samples, as well as a number of KS-free organs including the thyroid, salivary gland, and myocardium that have not been described before. Mutations in the viral DNA could be demonstrated in all patients. The mutations found were related more to that seen in AIDS-KS cases than that found in African endemic KS cases. HHV-8 sequences could be detected in follow-up frozen skin biopsies of five patients but were negative in the equivalent formalin-fixed specimens. Viral DNA was also detected in 2 of 11 peripheral blood mononuclear cell samples collected at the time of the follow-up skin biopsies. CONCLUSION: Reduction or withdrawal of immunosuppression allows the immune system to recover sufficiently to reduce viral replication with subsequent viral persistence and low grade viral replication that coincides with clinical remission of the KS lesions. This provides further evidence for the important etiological role played by HHV-8 in the pathogenesis of posttransplant KS.

Clinical experience with Repotin, a locally produced recombinant human erythropoietin, in the treatment of anaemia of chronic renal failure in South Africa.

OBJECTIVE: To evaluate the efficacy and safety of Repotin, a locally produced recombinant human erythropoietin (rHuEPO), in the treatment of the anaemia of chronic renal failure (ACRF). DESIGN: The study consisted of two multicentre non-randomised open stages. SETTING: Renal units at several teaching hospitals in South Africa. PARTICIPANTS: Haemodialysis patients with haemoglobin (Hb) levels less than 8.0 g/dl were recruited. The first stage examined 26 patients during a 12-week period in which the dose of intravenous rHuEPO was adjusted according to haematological response. In the second stage 27 patients were stabilised with intravenous rHuEPO and then maintained at a Hb level above 8.0 g/dl by subcutaneous administration for up to 1 year. OUTCOME MEASURES: In both stages, outcome was measured by clinical examination, blood pressure, full haematological parameters and blood chemistry. RESULTS: In stage 1, all patients responded to therapy with a statistically significant increase in Hb from geometric means of 6.28 g/dl to 8.50 g/dl (geometric SDs of 1.17 and 1.20 respectively). The doses used ranged from 25 IU to 125 IU/kg (average 47.1). In the second stage, Hb levels reached a mean of 8.06 g/dl (SD 0.9) and were maintained at target range with an average dose of 55.5 IU/kg three times a week. Apart from changes in serum iron, ferritin (associated with increased haematopoiesis) and potassium, there were no significant alterations in blood chemistry. The incidence of adverse events reported during the 12-month second stage was no greater than that reported for other forms of rHuEPO therapy. CONCLUSION: Repotin is a safe and effective rHuEPO preparation for the treatment of ACRF.

The prevalence of antibodies to hepatitis C virus at two haemodialysis units in South Africa.

The prevalence of antibodies against hepatitis C virus (HCV) was determined in 103 haemodialysis patients who attended two dialysis units in South Africa. With the use of a second-generation enzyme-linked immunosorbent assay (UBI HCV EIA, Organon Teknika, The Netherlands) and a 4-recombinant immunoblot assay (Chiron Corporation, USA), antibodies to HCV were found in 22 patients (21%). Statistically significant associations with anti-HCV carrier status were duration of dialysis (P = 0.0005) and number of blood transfusions received (P = 0.008). With stepwise logistic regression analysis it was not possible to separate the effects of HCV status associated with these two variables. A transient elevation in alanine aminotransferase (ALT) occurred in 8 of the 22 anti-HCV-positive patients, compared with 14 of the 81 anti-HCV-negative patients (P = 0.054). As yet, no patients have clinical evidence of ongoing liver disease or persistently elevated ALT levels. Of the 45 dialysis staff members tested, none was positive for anti-HCV.

Pulmonary complications in 110 consecutive renal transplant recipients.

The pulmonary complications in 110 consecutive renal transplant recipients on cyclosporin and low-dose steroid immunosuppression were studied retrospectively. The pulmonary complications were: acute pulmonary oedema in 19 patients, pneumonia in 18, tuberculosis in 9, acute pulmonary embolism in 5, and lung abscess in 1. Sixty-nine patients (62.7%) had no pulmonary complications; 69% of the complications occurred in the first 4 months after the transplant. Pulmonary tuberculosis became evident later. The mean age, period of follow-up, human leucocyte antigen (HLA) B/DR mismatches, mean serum urea and serum creatinine concentrations, systolic and diastolic blood pressures, and cyclosporin dosage did not differ between the groups with no complications, infectious complications and non-infectious complications. The number of rejection episodes treated with bolus steroids was significantly higher in the infectious and non-infectious complications groups compared with the group with no complications. The incidence of pulmonary complications after renal transplantation, especially pneumonia and tuberculosis, was still high despite the use of low-dose steroids and cyclosporin. Pulmonary complications were the commonest cause of death in the first 3 years after the transplant. A high index of suspicion for pulmonary tuberculosis and pulmonary embolism in these patients is necessary.