Hepatitis C and kidney disease: A narrative review.

Hepatitis-C (HCV) infection can induce kidney injury, mostly due to formation of immune-complexes and cryoglobulins, and possibly to a direct cytopathic effect. It may cause acute kidney injury (AKI) as a part of systemic vasculitis, and augments the risk of AKI due to other etiologies. It is responsible for mesangiocapillary or membranous glomerulonephritis, and accelerates the progression of chronic kidney disease due to other causes. HCV infection increases cardiovascular and liver-related mortality in patients on regular dialysis. HCV-infected patients are at increased risk of acute post-transplant complications. Long-term graft survival is compromised by recurrent or de novo glomerulonephritis, or chronic transplant glomerulopathy. Patient survival is challenged by increased incidence of diabetes, sepsis, post-transplant lymphoproliferative disease, and liver failure. Effective and safe directly acting antiviral agents (DAAs) are currently available for treatment at different stages of kidney disease. However, the relative shortage of DAAs in countries where HCV is highly endemic imposes a need for treatment-prioritization, for which a scoring system is proposed in this review. It is concluded that the thoughtful use of DAAs, will result in a significant change in the epidemiology and clinical profiles of kidney disease, as well as improvement of dialysis and transplant outcomes, in endemic areas.

Burden of end-stage kidney disease: North Africa.

Geographical, ecological, and genetic factors result in many similarities among the six main countries of the African Sahara, including the epidemiology of kidney disease. With an average incidence of 182 and prevalence of 522 patients with end-stage kidney disease (ESKD) per million population, North Africa (NA) spends $650 million on dialysis and transplantation despite an estimated annual loss of 600,000 life years. The health burden of ESKD is not limited to its directly-related morbidity and mortality but affects even more significantly other body systems, particularly the cardiovascular system. In addition, dialysis units are reservoirs for infectious agents, such as hepatitis-C (HCV) and -B (HBV) viruses, and methicillin-resistant staphylococci (MRSA), which threaten the health of the community. Shortage of financial resources eventually creates inequity of health care at large since only the rich are able to find their way around the limited public services. ESKD is no exception; inequity being even further augmented by the trade of organs, particularly in Egypt. This is attributed to high demand in the absence of a deceased donor program and in the presence of a pool of young, healthy, unemployed potential donors who have no access to any social security plans. Many attempts to face the challenge of accommodating ESKD management in NA are underway, including relevant legislations, promoting deceased donor transplants, chronic kidney disease (CKD) prevention and early detection programs, and generating nontraditionally directed financial resources.

Fifty years of dialysis in Africa: challenges and progress.

This review addresses the development of dialysis services in Africa in the face of past and contemporary challenges. Maintenance dialysis treatment programs developed in 29 countries over the past 50 years, usually many years after their independence and the end of subsequent territorial and civil wars. Eight countries had the resources to launch national dialysis programs, conventionally defined as those accommodating at least 100 patients per million population. Additionally, based on information obtained from international and local publications, conference proceedings, and personal communications, it appears that limited short-term dialysis therapy currently is available in most African countries. Currently, the prevalence of and outcomes associated with dialysis in Africa are influenced significantly by the following: (1) local health indexes, including the prevalence of undernutrition and chronic infections; (2) per capita gross domestic product; (3) national expenditures on health and growth of these expenditures with incremental demand; (4) availability and adequate training of health care providers; and (5) literacy. In an attempt to reduce the socioeconomic burden of maintenance dialysis treatment, 12 countries have adopted active transplantation programs and 5 are striving to develop screening and prevention programs. Our recommendations based on these observations include optimizing dialysis treatment initiatives and integrating them with other health strategies, as well as training and motivating local health care providers. These steps should be taken in collaboration with regulatory authorities and the public.

Parasitic kidney disease: milestones in the evolution of our knowledge.

Of the 342 parasites that infect humans, 20 are associated with kidney disease, yet of these, only schistosomes, plasmodia, filariae, and leishmanias are held responsible for significant clinical or epidemiologic impact. Reviewing the evolution of human knowledge for these parasites discloses a lot of similarities regarding their discovery, patterns of kidney injury, and pathogenic mechanisms. From a historical perspective, our relevant information may be classified into 4 phases: (1) disease documentation in ancient and medieval scripts as far back as 2000-3000 bce; (2) discovery of the parasites, their life cycles, and clinical correlates by European clinicians working in African and Asian colonies during the second half of the 19th century; (3) discovery and characterization of the renal manifestations of monoparasitic infections during the second half of the 20th century; and (4) recognition of the confounding effects of coinfection with bacteria, viruses, or other parasites. The spectrum of respective kidney diseases extends all the way from acute kidney injury to glomerulonephritis, amyloidosis, urologic disorders, and malignancy. Discovery of the common immunopathogenetic host response to parasitic infections has provided a knowledge core that explains the similarities, diversities, and interactions with regard to kidney injury.

Human schistosomiasis: clinical perspective: review.

The clinical manifestations of schistosomiasis pass by acute, sub acute and chronic stages that mirror the immune response to infection. The later includes in succession innate, TH1 and TH2 adaptive stages, with an ultimate establishment of concomitant immunity. Some patients may also develop late complications, or suffer the sequelae of co-infection with other parasites, bacteria or viruses. Acute manifestations are species-independent; occur during the early stages of invasion and migration, where infection-naivety and the host's racial and genetic setting play a major role. Sub acute manifestations occur after maturity of the parasite and settlement in target organs. They are related to the formation of granulomata around eggs or dead worms, primarily in the lower urinary tract with Schistosoma haematobium, and the colon and rectum with Schistosoma mansoni, Schistosoma japonicum, Schistosoma intercalatum and Schistosoma mekongi infection. Secondary manifestations during this stage may occur in the kidneys, liver, lungs or other ectopic sites. Chronic morbidity is attributed to the healing of granulomata by fibrosis and calcification at the sites of oval entrapment, deposition of schistosomal antigen-antibody complexes in the renal glomeruli or the development of secondary amyloidosis. Malignancy may complicate the chronic lesions in the urinary bladder or colon. Co-infection with salmonella or hepatitis viruses B or C may confound the clinical picture of schistosomiasis, while the latter may have a negative impact on the course of other co-infections as malaria, leishmaniasis and HIV. Prevention of schistosomiasis is basically geared around education and periodic mass treatment, an effective vaccine being still experimental. Praziquantel is the drug of choice in the treatment of active infection by any species, with a cure rate of 80%. Other antischistosomal drugs include metrifonate for S. haematobium, oxamniquine for S. mansoni and Artemether and, possibly, Mirazid for both. Surgical treatment may be needed for fibrotic lesions.

Urinary schistosomiasis: review.

UNLABELLED: In this review, the clinical manifestations of urinary schistosomiasis are displayed from a pathogenetic perspective. According to the prevailing host's immune response profile, urinary schistosomiasis may be broadly categorized into cell-mediated and immune-complex-mediated disorders. The former, usually due to Schistosoma haematobium infection, are attributed to the formation of granulomata along the entire urinary tract. As they heal with excessive fibrosis, they may lead to strictures, calcifications and urodynamic abnormalities. The main impact is lower urinary, the site of heaviest ovi-position. Secondary bacterial or viral infection is common, any may be incriminated in secondary stone formation of the development of bladder malignancy. Immune-complex mediated lesions are usually associated with hepatosplenic schistosomiasis due to Schistosoma mansoni infection. Circulating complexes composed of schistosomal gut antigens and different classes of immunoglobulins deposit in the kidneys leading to several patterns of glomerular pathology. The latter have been categorized under six classes based on the histological and immunofluorescence profile. These classes have been linked to respective clinical manifestations and depend on the stage of evolution of the host's immune response, extent of associated hepatic fibrosis and co-infection with salmonella or hepatitis C. Secondary amyloidosis develops in 15% of such patients, representing a critical impairment of macrophage function. CONCLUSION: The wide clinicopathological spectrum of urinary schistosomiasis mirrors the evolution of the host's immune response according to chronicity of infection, bacterial or viral co-infection and, in the case of glomerulonephritis, to the extent of hepatic co-morbidity.

Burden of chronic kidney disease: North Africa.

North Africa (NAF) is composed of six countries located in the African Sahara, namely the Western Sahara, Morocco, Algeria, Tunisia, Libya, and Egypt. Common features between these countries include similar climate, ecology, population genetics, and the socioeconomic environment. This commonality reflects on the chronic kidney disease (CKD) profile in these countries. While there are some estimates on the epidemiology of end-stage kidney disease, that of earlier stages is unknown. Several national screening programs are currently addressing this issue, such as the EGIPT-CKD project in Egypt and the MAREMAR study in Morocco. Preliminary results from the former suggest a prevalence of proteinuria in 10.6% of the relatives of patients on regular dialysis treatment. Despite the lack of reliable registries, it was possible to gather information on the etiology of CKD by direct contact with leading nephrologists in those countries. It turns out that glomerulonephritis (GN) accounts for 9-20%, diabetes 11-18%, hypertensive nephrosclerosis 10-35%, chronic interstitial nephritis 7-17%, and polycystic disease 2-3%. Compared to two decades earlier, diabetes has become more common at the expense of GN, proliferative GN, and amyloidosis regressed in favor of IgA and membranous nephropathies in Tunisian adults. Conventional schistosomal nephropathies are regressing in favor of hepatitis C viral (HCV) nephropathy in Egyptians. Focal segmental glomerulosclerosis is increasing at the expense of proliferative GNs in the region at large. Access to regular dialysis has been optimized during the past decade, with favorable outcomes despite the high incidence of HCV infection, tuberculosis, and protein-calorie malnutrition. Kidney transplantation is available in all NAF countries except the Western Sahara. About 650 transplants are performed annually from live donors, the majority in Egypt, where data from the largest center in Mansoura display a 10-year graft survival of 62%. Many transplants are performed from living unrelated donors, particularly in Egypt, which creates an ethical debate. Legislation for deceased-donor transplantation has been passed successively over the past two decades in Tunisia, Morocco, Algeria, and Egypt, which is expected to reflect quantitatively and qualitatively on the transplantation activity in the near future.

A mission in evolution: the International Society of Nephrology in the past 10 years--2001-2010.

The International Society of Nephrology is now 50 years old! It has dedicated the year 2010 to celebrate its Gold Anniversary in many ways, including documentation of its progress during the past decade, following an earlier article addressing the period 1960-2000. The present article describes the changing mission of the Society in the direction of achieving its ultimate vision of "global elimination of kidney disease." While maintaining its leadership in the promotion of science, it became the prime driving force in capacity building for the diagnosis, prevention and management of kidney disease in the developing world. The society has recently modified its directive from addressing only the physicians providing renal care to supporting other health care providers, and sharing in community education on how to avoid kidney disease. This required the acquisition of new skills in publishing, marketing, politics and fund-raising, which could only be handled by professional management, which the Society has utilized since 2003. It also necessitated enlargement of the leadership circle to include members from all over the world, for which reason the constitution had to be amended twice during the past decade, and the bylaws re-written in 2007. The pride that International Society of Nephrology takes from its scientific and outreach achievements is the fuel that drives its machinery to endless horizons in the humanitarian arena.

Trends in unrelated-donor kidney transplantation in the developing world.

Living unrelated donors (LUDs) constitute an incremental source of kidneys for transplantation at a global level. Excellent outcomes are reported, superior to those of deceased-donor transplantation and comparable to related donor transplantation. LUD include six categories: spouses, distant relatives, paired-exchange, living-deceased exchange, and non-directed and directed donors. Although a financial reward may be involved in any of these categories, it is in the declared selling of organs that ethical concerns have intensified. There are three patterns of paid LUDs in the developing world: organized, erratic and commercial. The only model of organized LUDs is in Iran, where a central agency assigns and compensates the donors. Erratic LUD transplantation has been experienced, and subsequently banned, in the development of transplant programmes in most developing countries. However, the tightness and enforcement of the official ban are geographically different, providing variable room for uncontrolled trafficking. Commercial transplantation has, thus, become phenomenal in a few countries, gradually evolving into an organized business that follows market dynamics, including advertisement, brokerage, commissions, auctions and tourism. While most international organizations and activist groups condemn commercial transplantation, it is often perceived, in certain cultures and under particular socioeconomic standards, as a human right that meets the demands of all stakeholders, and should be organized rather than declined just for the purpose of meeting the values of a third party.

CKD prevention in Sub-Saharan Africa: a call for governmental, nongovernmental, and community support.

The upsurge in incidence and prevalence of chronic kidney disease (CKD) in both developed and developing nations has necessitated a renewed interest in global CKD prevention because it is now regarded as a public health threat. Although CKD management is consuming a huge proportion of health care finances in developed countries, it is contributing significantly to morbidity, mortality, and decreased life expectancy in developing ones. CKD epidemiological characteristics in Sub-Saharan Africa (SSA) are strikingly different from those observed in other regions. Although middle-aged and elderly populations are predominantly affected in developed countries, in SSA, CKD mainly affects young adults in their economically productive years, with hypertension and infection-related chronic glomerulonephritis as the major causes. Morbidity and mortality are high because most affected individuals cannot access renal replacement therapy. Other contributory factors for this dismal picture include late presentation, limited renal replacement therapy and its unaffordability, absence of kidney disease prevention programs, and the poor literacy level. This gloomy outlook of CKD in the subregion makes prevention the only viable option in the long term while struggling to improve access to renal replacement therapy in the short term. Unfortunately, most countries in SSA have no prevention programs, and where available, they are either institutions or individual based with very little or no governmental support. This review focuses on the burden of CKD in SSA and reviews the available prevention programs with a view to stimulating governments, communities, and organizations to establishing an inexpensive and affordable program in the entire subregion.

The Cairo kidney center protocol for rapamycin-based sequential immunosuppression in kidney transplant recipients: 2-year outcomes.

OBJECTIVE: This study examines the outcomes of de novo kidney transplants treated by a sequential protocol, designed to target the succession of immunologic events following engraftment. SUBJECTS: A total of 113 sequential live-donor recipients were randomized into 2 arms. Patients in arm A received prednisolone, cyclosporine, and sirolimus for 3 months (phase 1), followed by replacement of cyclosporine with mycophenolate mofetil (phase 2). Those in arm B (controls) received prednisolone/cyclosporine/mycophenolate mofetil throughout the study. The primary endpoints were patient and graft survival rates at 2 years. Secondary endpoints included biopsy-proven acute rejection, early and late graft function, hypertension, and adverse reactions. RESULTS: The 2-year intent-to-treat patient and graft survival rates (95.8% vs 91.4% and 94.6% vs 90.2%) were numerically but not significantly higher in arm A. The overall incidence of biopsy-proven acute rejection was numerically lower (13.5% vs 18.9%), yet it occurred exclusively with cyclosporine C2 levels below 770 ng/mL (P = .28). Mean time for serum creatinine to reach 132 micromol/L was significantly longer in arm A (7.3 vs 2.9 days). Graft function at 2 years (eGFR, 70.2 vs 55.9 mL/min) and number of drugs needed to control blood pressure (mean 1.7 vs 2.25) were significantly more favorable in group A. Significant adverse effects for patients in arm A included proteinuria (36.8% vs 18.6%), hyperlipidemia (peak cholesterol > 7.75 mmol/L in 32.9% vs 23.7% of patients) and thrombocytopenia (platelet count < 100 x 109/L in 32.9% vs 13.5 % of patients). CONCLUSIONS: The described protocol reduced the incidence of biopsy-proven acute rejection in patients after kidney transplant, particularly in those with adequate cyclosporine blood levels. Despite the significantly higher incidence of certain adverse effects (ie, delayed graft function, proteinuria, hyperlipidemia, and transient thrombocytopenia), patient and graft survival rates at 2 years were numerically, though not statistically, improved in patients in arm A. At 2-year analysis, compared with patients in the control arm (arm B), graft function significantly improved in patients in arm A, and the number of drugs needed to control blood pressure was significantly lower.

Parasitic infections in transplant recipients.

Parasitic infections are important complications of organ transplantation that are often overlooked in the differential diagnosis of post-transplantation pyrexial illness. Although their frequency is unknown, they seem to be much less prevalent than bacterial and viral infections. Only 5% of human pathogenic parasites have been reported to cause significant illness in transplant recipients. Infection can occur via transmission with the graft or blood transfusion, or be acquired de novo from the environment. Recrudescence of dormant infection can lead to active disease. Post-transplantation parasitic disorders tend to cluster into two clinical profiles. First, an acute systemic illness with anemia, constitutional manifestations and variable stigmata of organ involvement; acute graft dysfunction can lead to confusion and acute rejection. Protozoa including malarial Plasmodium, Leishmania, Trypanosoma and Toxoplasma are associated with this profile. The second typical manifestation encompasses a few localized syndromes, usually associated with the lower gastrointestinal tract, caused by either protozoa (Cryptosporidium and microsporidia) or nematodes (Strongyloides and Ascaris). Dissemination of localized infections can lead to life-threatening systemic manifestations. A high index of suspicion is essential, as diagnosis requires special sampling techniques and laboratory procedures. Definitive diagnosis is usually achieved by detecting the parasite in the patient's tissues or body fluids by histological examination or culture, or by polymerase chain reaction amplification of the parasite-specific antigen sequence. Antibody detection using serological techniques is also possible in a few parasitic infections. Certain lesions have characteristic radiological appearances, hence the value of imaging, particularly in the cerebral syndromes. Treatment is usually straightforward (broad spectrum or specific drugs), yet some species are drug resistant.

Indices for assessment of hemodialysis adequacy: a comparison of different formulae.

Of the various indices used in the assessment of dialysis adequacy, fractional urea clearance controlled for volume of distribution "Kt/V" remains the most widely used. Its determination is best performed by formal urea kinetic modeling (UKM), which is laborious and cumbersome, and the computational softwares are largely unavailable, particularly in developing countries. Consequently, different equations have been developed that approximate the formal UKM determination. Of the available formulae, that from second-generation logarithmic equation have been found to approximate values derived from formal UKM closely. We set out to determine the clinical utility of percent reduction of urea and Kt/V formulae derived from it, using the logarithmic equation as the standard.

Correlation between Karnofsky Performance Status Scale and Short-Form Health Survey in patients on maintenance hemodialysis.

BACKGROUND: Assessment of quality of life is vital inmonitoring response to various treatment measures. Various instruments, which include both generic and disease-specific instruments, are used in the assessment of health-related quality of life (HRQOL). In this study, we compare two commonly used generic instruments. OBJECTIVES: The objective of this study was to compare two generic instruments, the Karnofsky Performance Status Scale and the SF-36 Health Survey in hemodialysis (HD) patients. The study also aims to find out the association (if any) between HRQOL scores using these two scales and various clinical and biochemical parameters. MATERIALS AND METHODS: Sixty-two maintenance HD patients were recruited after informed consents were obtained. Detailed sociodemographic data was obtained. They were assessed during their regular HD sessions. Serum chemistry (which included serum urea, creatinine, Na+, K+, HCO3-, Ca2+, Po4(2-)), albumin, globulin, total protein and hemoglobin (g/dl) were assessed in all the patients. Adequacy of HD was assessed using second-generation Daugirdais formula. HRQOL was assessed using the Karnofsky and SSF-36 instruments and the scores collated and compared. Data was analyzed using SPSS version 10. RESULTS: Fifty-five patients completed the study (27 males and 28 females, mean age 40.76 +/- 11.05 years and age range of 20-65 years). There was a significant positive correlation between Karnofsky scores and all eight SF-36 domains, but only physical functioning, social functioning and role limitation due to emotional problems maintained the significance on multiple regression analysis. The serum creatinine and hemoglobin postively correlated with physical function, bodily pain, social functioning and Karnofsky scores. Age of the patients correlated negatively with two SF-36 dimensions (physical functioning and role limitation due to physical fitness) and Karnofsky scores. CONCLUSION: This study revealed a good correlation between Karnofsky performance status scale and the short-form (SF36) health survey in this Egyptian population. Age, serum creatinine and hemoglobin significantly influence quality of life in this HD patient population.

Parasitic infections in organ transplantation.

More than 340 parasitic species infect more than 3 billion people worldwide with varying morbidity and mortality. The Tropics constitute the main reservoir of infection with the highest clinical impact, owing to favorable ecological factors. Acquisition of infection, clinical severity, and outcome of a parasitic disease depend on innate and acquired host immunity as well as the parasite's own immune response against the host when infection is established. Organ transplant recipients may acquire significant parasitic disease in 3 ways: transmission with the graft, de novo infection, or activation of dormant infection as a consequence of immunosuppression. Malaria, Trypanosoma, Toxoplasma, and Leishmania are the principal parasites that may be transmitted with bone marrow, kidney, or liver homografts, and microsporidia with xenotransplants. De novo infection with malaria and kala-azar may occur in immunocompromised travelers visiting in endemic areas, while immunocompromised natives are subject to superinfection with different strains of endemic parasites, reinfection with schistosomiasis, or rarely, with primary infections such as acanthamoeba. The list of parasites that may be reactivated in the immunocompromised host includes giardiasis, balantidiasis, strongyloidiasis, capillariasis, malaria, Chagas' disease, and kalaazar. The broad clinical syndromes of parasitic infection in transplant recipients include prolonged pyrexia, lower gastrointestinal symptoms, bronchopneumonia, and meningoencephalitis. Specific syndromes include the hematologic manifestations of malaria, myocarditis in Chagas' disease, acute renal failure in malaria and leishmaniasis, and the typical skin lesions of Chagas' and cutaneous leishmaniasis. Many antiparasitic drugs have the potential for gastrointestinal, hepatic, renal, and hematologic toxicity, and may interact with the metabolism of immunosuppressive agents. It is recommended that transplant clinicians have a high index of suspicion of parasitic infections as an important transmission threat, as well as a potential cause of significant posttransplant morbidity.