Saraladevi Naicker

Chronic kidney disease: global dimension and perspectives

Chronic kidney disease is defined as a reduced glomerular filtration rate, increased urinary albumin excretion, or both, and is an increasing public health issue. Prevalence is estimated to be 8-16% worldwide. Complications include increased all-cause and cardiovascular mortality, kidney-disease progression, acute kidney injury, cognitive decline, anaemia, mineral and bone disorders, and fractures. Worldwide, diabetes mellitus is the most common cause of chronic kidney disease, but in some regions other causes, such as herbal and environmental toxins, are more common. The poorest populations are at the highest risk. Screening and intervention can prevent chronic kidney disease, and where management strategies have been implemented the incidence of end-stage kidney disease has been reduced. Awareness of the disorder, however, remains low in many communities and among many physicians. Strategies to reduce burden and costs related to chronic kidney disease need to be included in national programmes for non-communicable diseases.

Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients.

BACKGROUND The efficacy of tenofovir disoproxil fumarate (TDF) as part of combination antiretroviral treatment (ART) has been demonstrated in several randomized, controlled trials. However, an increasing number of case reports suggest that TDF use may be associated with significant nephrotoxicity. Our objective was to determine the renal safety of TDF-containing ART regimens for HIV-infected individuals. METHODS MEDLINE, EMBASE, Global Health, Scopus, Biosis Previews, Cochrane Library, Web of Science, and existing systematic reviews were searched. Prospective studies comparing TDF-containing with non-TDF containing ART regimens were selected for inclusion. We extracted data on study characteristics, participant characteristics, therapeutic interventions, renal function, bone density, and fracture rates. RESULTS A total of 17 studies (including 9 randomized, controlled trials) met the selection criteria. Median sample size was 517 participants. Constituent ART regimens were diverse. There was a significantly greater loss of kidney function among the TDF recipients, compared with control subjects (mean difference in calculated creatinine clearance, 3.92 mL/min; 95% confidence interval [CI], 2.13-5.70 mL/min), as well as a greater risk of acute renal failure (risk difference, 0.7%; 95% CI, 0.2-1.2). There was no evidence that TDF use led to increased risk of severe proteinuria, hypophosphatemia, or fractures. CONCLUSIONS Although TDF use was associated with a statistically significant loss of renal function, the clinical magnitude of this effect was modest. Our findings do not support the need to restrict TDF use in jurisdictions where regular monitoring of renal function and serum phosphate levels is impractical.

Guidelines for the treatment and management of new-onset diabetes after transplantation.

Abstract:  Although graft and patient survival after solid organ transplantation have improved markedly in recent years, transplant recipients continue to experience an increased prevalence of cardiovascular disease (CVD) compared with the general population. A number of factors are known to impact on the increased risk of CVD in this population, including hypertension, dyslipidemia and diabetes mellitus. Of these factors, new‐onset diabetes after transplantation has been identified as one of the most important, being associated with reduced graft function and patient survival, and increased risk of graft loss. In 2003, International Consensus Guidelines on New‐onset Diabetes after Transplantation were published, which aimed to establish a precise definition and diagnosis of the condition and recommend management strategies to reduce its occurrence and impact. These updated 2004 guidelines, developed in consultation with the International Diabetes Federation (IDF), extend the recommendations of the previous guidelines and encompass new‐onset diabetes after kidney, liver and heart transplantation. It is hoped that adoption of these management approaches pre‐ and post‐transplant will reduce individuals’ risk of developing new‐onset diabetes after transplantation as well as ameliorating the long‐term impact of this serious complication.

Executive summary of the KDIGO Controversies Conference on Supportive Care in Chronic Kidney Disease: developing a roadmap to improving quality care

Patients with advanced chronic kidney disease (CKD) have a high burden of physical and psychosocial symptoms, poor outcomes, and high costs of care. Current paradigms of care for this highly vulnerable population are variable, prognostic and assessment tools are limited, and quality of care, particularly regarding conservative and palliative care, is suboptimal. The KDIGO Controversies Conference on Supportive Care in CKD reviewed the current state of knowledge in order to define a roadmap to guide clinical and research activities focused on improving the outcomes of people living with advanced CKD, including those on dialysis. An international group of multidisciplinary experts in CKD, palliative care, methodology, economics, and education identified the key issues related to palliative care in this population. The conference led to a working plan to address outstanding issues in this arena, and this executive summary serves as an output to guide future work, including the development of globally applicable guidelines.

The epidemiology of chronic kidney disease in sub-Saharan Africa: a systematic review and meta-analysis

BACKGROUND Amid rapid urbanisation, the HIV epidemic, and increasing rates of non-communicable diseases, people in sub-Saharan Africa are especially vulnerable to kidney disease. Little is known about the epidemiology of chronic kidney disease (CKD) in sub-Saharan Africa, so we did a systematic review and meta-analysis examining the epidemiology of the disease. METHODS We searched Medline, Embase, and WHO Global Health Library databases for all articles published through March 29, 2012, and searched the reference lists of retrieved articles. We independently reviewed each study for quality. We used the inverse-variance random-effects method for meta-analyses of the medium-quality and high-quality data and explored heterogeneity by comparing CKD burdens across countries, settings (urban or rural), comorbid disorders (hypertension, diabetes, HIV), CKD definitions, and time. FINDINGS Overall, we included 90 studies from 96 sites in the review. Study quality was low, with only 18 (20%) medium-quality studies and three (3%) high-quality studies. We noted moderate heterogeneity between the medium-quality and high-quality studies (n=21; I(2)=47·11%, p<0·0009). Measurement of urine protein was the most common method of determining the presence of kidney disease (62 [69%] studies), but the Cockcroft-Gault formula (22 [24%] studies) and Modification of Diet in Renal Disease formula (17 [19%] studies) were also used. Most of the studies were done in urban settings (83 [93%] studies) and after the year 2000 (57 [63%] studies), and we detected no significant difference in the prevalence of CKD between urban (12·4%, 95% CI 11-14) and rural (16·5%, 13·8-19·6) settings (p=0·474). The overall prevalence of CKD from the 21 medium-quality and high-quality studies was 13·9% (95% CI 12·2-15·7). INTERPRETATION In sub-Saharan Africa, CKD is a substantial health burden with risk factors that include communicable and non-communicable diseases. However, poor data quality limits inferences and draws attention to the need for more information and validated measures of kidney function especially in the context of the growing burden of non-communicable diseases. FUNDING Duke University.

APOL1 Risk Variants Are Strongly Associated with HIV-Associated Nephropathy in Black South Africans

APOL1 variants are associated with HIV-associated nephropathy and FSGS in African Americans. The prevalence of these variants in African populations with CKD in HIV-1 infection has not been investigated. We determined the role of APOL1 variants in 120 patients with HIV-associated nephropathy and CKD and 108 controls from a South-African black population. Patients with CKD were selected on the basis of histology. Genotypes were successfully determined for APOL1 G1 and G2 variants and 42 single nucleotide polymorphisms, including 18 ancestry informative markers, for 116 patients with CKD (96.7%; 38 patients with HIV-associated nephropathy, 39 patients with HIV-positive CKD, and 39 patients with HIV-negative CKD), and 108 controls (100%). Overall, 79% of patients with HIV-associated nephropathy and 2% of population controls carried two risk alleles. In a recessive model, individuals carrying any combination of two APOL1 risk alleles had 89-fold higher odds (95% confidence interval, 18 to 912; P<0.001) of developing HIV-associated nephropathy compared with HIV-positive controls. Population allele frequencies were 7.3% for G1 and 11.1% for G2. APOL1 risk alleles were not significantly associated with other forms of CKD. These results indicate HIV-positive, antiretroviral therapy-naïve South-African blacks with two APOL1 risk alleles are at very high risk for developing HIV-associated nephropathy. Further studies are required to determine the effect of APOL1 risk variants on kidney diseases in other regions of sub-Saharan Africa.

Epidemiology of Acute Kidney Injury in Africa

Acute kidney injury (AKI) is a challenging problem in Africa because of the burden of disease (especially human immunodeficiency virus [HIV]-related AKI in sub-Saharan Africa, diarrheal disease, malaria, and nephrotoxins), late presentation of patients to health care facilities, and the lack of resources to support patients with established AKI in many countries. The pattern of AKI is vastly different from that in more developed countries. There are no reliable statistics about the incidence of AKI in Africa. Infections (malaria, HIV, diarrheal diseases, and others), nephrotoxins, and obstetric and surgical complications are the major etiologies in Africa. AKI in hospitalized antiretroviral therapy (ART)-naive HIV-1-infected patients is associated with a 6-fold higher risk of in-hospital mortality. The most common risk factors are severe immunosuppression (CD4 count, <200 cells/mm(3)) and opportunistic infection. The most common causes are acute tubular necrosis and thrombotic microangiopathy. In the post-ART era, HIV-1-infected patients with AKI still have an increased risk of in-hospital mortality and these episodes of AKI seem more frequent in the first year of ART. Subsequently, survival is comparable in those with and without HIV infection. More resources are required to prevent AKI and to provide renal support for those patients requiring dialytic therapy.

Acute kidney injury associated with the use of traditional medicines

The use of traditional medicine is common worldwide, with rates of use of over 80% in some populations. Considering the large number of people using traditional remedies throughout the world, it does seem that most do so without major adverse effects. Nevertheless, many folk medicines can cause kidney injury. Drug-induced nephrotoxicity reportedly contributes to up to 26% of cases of hospital-acquired acute kidney injury (AKI) and 18% of cases of community-acquired AKI globally, and folk remedies account for up to 35% of cases of AKI in the developing world. The kidney is highly susceptible to toxic insults because its intrinsic functions expose it to exceptionally high concentrations of any particular toxic substance. Clinical syndromes of nephrotoxicity can be defined according to the predominant regions of the kidney affected by the toxin, and reversibility of the injury is likely related to the severity and nature of the injury and also to the duration of toxin exposure. In countries with well-developed health-care systems, a large proportion of patients with nephrotoxicity will recover at least some renal function with adequate supportive care and dialysis. Health-care practitioners in all countries should be aware of the high prevalence of the use of alternative therapies and should be proactive in obtaining this information from patients. In poorer countries, where large proportions of the population rely on traditional medicine, attempts should be made to integrate traditional healers into the health-care system.

HIV-associated nephropathies: epidemiology, pathology, mechanisms and treatment

HIV is a highly adaptive, rapidly evolving virus, which is associated with renal diseases including collapsing glomerulopathy—the classic histomorphological form of HIV-associated nephropathy. Other nephropathies related to viral factors include HIV-immune-complex kidney disease and thrombotic microangiopathy. The distribution of HIV-associated kidney diseases has changed over time and continues to vary across geographic regions worldwide. The reasons for this diversity are complex and include a critical role of APOL1 variants and possibly other genetic factors, disparities in access to effective antiviral therapies, and likely other factors that we do not yet fully understand. The mechanisms responsible for HIVAN, including HIV infection of podocytes and tubular epithelial cells, the molecules responsible for HIV entry, and diverse mechanisms of cell injury, have been the focus of much study. Although combined antiretroviral therapy is effective at preventing and reversing HIVAN, focal segmental glomerulosclerosis, arterionephrosclerosis and diabetic nephropathy are increasingly common in individuals who have received such therapy for many years. These diseases are associated with metabolic syndrome, obesity and premature ageing. Future directions for HIV-related kidney disease will involve regular screening for drug nephrotoxicity and incipient renal disease, as well as further research into the mechanisms by which chronic inflammation can lead to glomerular disease.

Organ trafficking and transplant tourism: the role of global professional ethical standards-the 2008 Declaration of Istanbul.

By 2005, human organ trafficking, commercialization, and transplant tourism had become a prominent and pervasive influence on transplantation therapy. The most common source of organs was impoverished people in India, Pakistan, Egypt, and the Philippines, deceased organ donors in Colombia, and executed prisoners in China. In response, in May 2008, The Transplantation Society and the International Society of Nephrology developed the Declaration of Istanbul on Organ Trafficking and Transplant Tourism consisting of a preamble, a set of principles, and a series of proposals. Promulgation of the Declaration of Istanbul and the formation of the Declaration of Istanbul Custodian Group to promote and uphold its principles have demonstrated that concerted, strategic, collaborative, and persistent actions by professionals can deliver tangible changes. Over the past 5 years, the Declaration of Istanbul Custodian Group organized and encouraged cooperation among professional bodies and relevant international, regional, and national governmental organizations, which has produced significant progress in combating organ trafficking and transplant tourism around the world. At a fifth anniversary meeting in Qatar in April 2013, the DICG took note of this progress and set forth in a Communiqué a number of specific activities and resolved to further engage groups from many sectors in working toward the Declaration’s objectives.