Egyptian clinical practice guideline for kidney transplantation.

Objective: To present the first Egyptian clinical practice guideline for kidney transplantation (KT). Methods: A panel of multidisciplinary subspecialties related to KT prepared this document. The sources of information included updates of six international guidelines, and review of several relevant international and Egyptian publications. All statements were graded according to the strength of clinical practice recommendation and the level of evidence. All recommendations were discussed by the panel members who represented most of the licensed Egyptian centres practicing KT. Results: Recommendations were given on preparation, surgical techniques and surgical complications of both donors and recipients. A special emphasis was made on the recipient's journey with immunosuppression. It starts with setting the scene by covering the donor and recipient evaluations, medicolegal requirements, recipient's protective vaccines, and risk assessment. It spans desensitisation and induction strategies to surgical approach and potential complications, options of maintenance immunosuppression, updated treatment of acute rejection and chemoprophylactic protocols. It ends with monitoring for potential complications of the recipient's suppressed immunity and the short- and long-term complications of immunosuppressive drugs. It highlights the importance of individualisation of immunosuppression strategies consistent with pre-KT risk assessment. It emphasises the all-important role of anti-human leucocyte antigen antibodies, particularly the donor-specific antibodies (DSAs), in acute and chronic rejection, and eventual graft and patient survival. It addresses the place of DSAs across the recipient's journey with his/her gift of life. Conclusion: This guideline introduces the first proposed standard of good clinical practice in the field of KT in Egypt. Abbreviations: Ab: antibody; ABMR: Ab-mediated rejection; ABO: ABO blood groups; BKV: BK polyomavirus; BMI: body mass index; BTS: British Transplantation Society; CAN: chronic allograft nephropathy; CDC: complement-dependent cytotoxicity; CKD: chronic kidney disease; CMV: cytomegalovirus; CNI: calcineurin inhibitor; CPRA: Calculated Panel Reactive Antibodies; (dn)DSA: (de novo) donor-specific antibodies; ECG: electrocardiogram; ESWL: extracorporeal shockwave lithotripsy; FCM: flow cytometry; GBM: glomerular basement membrane; GN: glomerulonephritis; HIV: human immunodeficiency virus; HLA: human leucocyte antigen; HPV: human papilloma virus; IL2-RA: interleukin-2 receptor antagonist; IVIg: intravenous immunoglobulin; KT(C)(R): kidney transplantation/transplant (candidate) (recipient); (L)(O)LDN: (laparoscopic) (open) live-donor nephrectomy; MBD: metabolic bone disease; MCS: Mean channel shift (in FCM-XM); MFI: mean fluorescence intensity; MMF: mycophenolate mofetil; mTOR(i): mammalian target of rapamycin (inhibitor); NG: 'not graded'; PAP: Papanicolaou smear; PCN: percutaneous nephrostomy; PCNL: percutaneous nephrolithotomy; PKTU: post-KT urolithiasis; PLEX: plasma exchange; PRA: panel reactive antibodies; PSI: proliferation signal inhibitor; PTA: percutaneous transluminal angioplasty; RAS: renal artery stenosis; RAT: renal artery thrombosis;:rATG: rabbit anti-thymocyte globulin; RCT: randomised controlled trial; RIS: Relative MFI Score; RVT: renal vein thrombosis; TB: tuberculosis; TCMR: T-cell-mediated rejection; URS: ureterorenoscopy; (CD)US: (colour Doppler) ultrasonography; VCUG: voiding cystourethrogram; XM: cross match; ZN: Ziehl-Neelsen stain.

Hepatitis C virus infection and global kidney health: the consensus proceedings of the International Federation of Kidney Foundations.

Hepatitis C virus (HCV) infection is an important cause of major morbidities including chronic liver disease, liver cancer, and acute kidney injury (AKI) as well as chronic kidney disease (CKD). HCV can affect kidney health; among CKD and AKI patients with HCV infection, the clinical outcomes are worse. The prevalence of HCV infection is exceptionally high among dialysis and kidney transplant patients throughout the globe. It is estimated that 5% to 25% or more of dialysis dependent patients are affected by chronic HCV, based on the region of the world. Almost half of all deaths in CKD patients, including HCV-infected patients, are due to cardiovascular disease, and HCV infected patients have higher mortality. Given the importance and impact of the HCV epidemic on CKD and global kidney health, and the status of Egypt as the nation with highest prevalence of HCV infection in the world along with its leading initiatives to eradicate HCV, the International Federation of Kidney Foundations (IFKF) convened a consensus conference in Cairo in December 2017. This article reflects the opinions and recommendations of the contributing experts and reiterates that with the current availability of highly effective and well tolerated pharmacotherapy; CKD patients should be given priority for treatment of HCV, as an important step towards the elimination of viral hepatitis as a public health problem by 2030 according to World Health Organization and IFKF. Every country should have an action plan with the goal to improve kidney health and CKD patient outcomes.

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.

Antiviral treatment prioritization in HCV-infected patients with extrahepatic manifestations - An Egyptian perspective.

Egypt, the single country with highest incidence of HCV infection in the world, has embarked on a government-sponsored mass treatment program using several combinations of DAAs. Recognizing the importance of extrahepatic manifestations, independently of the hepatic, a subcommittee was assigned to develop national guidelines for respective prioritizing indications and protocols. It evaluated the benefit of treating patients with different extrahepatic manifestations, and reviewed relevant clinical trials and guidelines concerning DAA combinations available in Egypt. The latter included Sofosbuvir plus either peg-interferon, Simeprevir, Ledipasvir or daclatasvir, and the Viekera family comprising paritaprevir/ritonavir + ombitasvir with (GT-1) or without (GT-4) Dasabuvir. Any of these protocols may be used with or without Ribavirin according to indication. A blueprint was subjected to peer debate in dedicated workshops in two national meetings and subsequently to an online professional review, eventually leading to a final report that was adopted by the health authorities. Seven compelling and 10 optional indications were identified for treating patients with predominantly extrahepatic manifestations. The former include kidney disease at different stages, cryoglobulinemic vasculitis and non-Hodgkin lymphoma. Selected treatment protocols, were encoded and their use was prioritized on the basis of evidence of efficacy and safety. We concluded that any of the studied protocols may be used, preferably with ribavirin, for 12-week treatment in all patients with extrahepatic manifestations without cirrhosis and with eGFR above 30 ml/min/1.73 sqm. Ribavirin should be included in protocols for treating patients with compensated cirrhosis. Daclatasvir-based protocols are recommended for decompensated cirrhosis, while the Viekera family is recommended in patients with eGFR < 30 ml/min/1.73 sqm, including those on dialysis. In kidney-transplanted patents, caution is due to avoidance of the pharmacokinetic interaction with the Cytochrome-P450 enzyme system, in-between immunosuppressive agents and most DAAs, particularly the Viekera family.

Eight-year outcomes of 'the Cairo Kidney Centre sequential protocol'.

OBJECTIVES: To describe the long-term results of a previously developed a sirolimus-based sequential immunosuppression protocol for kidney transplant comprising 2 phases: sirolimus + cyclosporine + prednisolone for 3 months followed by sirolimus + prednisolone + mycophenolate mofetil with steroid minimization the first year. Two-year outcomes of patients on this protocol (group A) showed equivalent patient and graft survival, yet with significantly better function, compared with those on cyclosporine + mycophenolate mofetil + prednisolone (group B). MATERIALS AND METHODS: We report the 8-year outcomes in the same cohort (76 patients in group A and 37 in group B). RESULTS: 42% switched from group A to B versus 43% switching from B to A. Intent-to-treat patient survivals at 5 and 8 years were 88% and 85.5% for group A, and 78% and 73% for group B. Death-censored graft survivals were 93% for group A and 95% for group B. Graft function was significantly better at 8 years, with 91% of group A patients compared with 50% in group B having estimated glomerular filtration rates > 45 mL/min/1.73 m2, and a significantly lower incidence of chronic allograft nephropathy in the former. Secondary parameters including blood pressure control, new onset diabetes mellitus, proteinuria and other drug-related adverse events showed no significant differences between the groups. CONCLUSIONS: The sirolimus-based sequential immunosuppression protocol was well tolerated in 58% of patients. The intent-to-treat and patients-ontherapy analyses revealed that it was equivalent to the widely used cyclosporine + mycophenolate mofetil + prednisolone protocol regarding patient and graft survival. It is associated with better graft function and lower incidence of chronic allograft nephropathy in 8 years' follow-up. The incidence of drug-related adverse reactions was not statistically different from those in the comparator.

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.

Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data.

OBJECTIVE: To examine risk of malignancy and death in patients with kidney transplant who receive the immunosuppressive drug sirolimus. DESIGN: Systematic review and meta-analysis of individual patient data. DATA SOURCES: Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2013. ELIGIBILITY: Randomized controlled trials comparing immunosuppressive regimens with and without sirolimus in recipients of kidney or combined pancreatic and renal transplant for which the author was willing to provide individual patient level data. Two reviewers independently screened titles/abstracts and full text reports of potentially eligible trials to identify studies for inclusion. All eligible trials reported data on malignancy or survival. RESULTS: The search yielded 2365 unique citations. Patient level data were available from 5876 patients from 21 randomized trials. Sirolimus was associated with a 40% reduction in the risk of malignancy (adjusted hazard ratio 0.60, 95% confidence interval 0.39 to 0.93) and a 56% reduction in the risk of non-melanoma skin cancer (0.44, 0.30 to 0.63) compared with controls. The most pronounced effect was seen in patients who converted to sirolimus from an established immunosuppressive regimen, resulting in a reduction in risk of malignancy (0.34, 0.28 to 0.41), non-melanoma skin cancer (0.32, 0.24 to 0.42), and other cancers (0.52, 0.38 to 0.69). Sirolimus was associated with an increased risk of death (1.43, 1.21 to 1.71) compared with controls. CONCLUSIONS: Sirolimus was associated with a reduction in the risk of malignancy and non-melanoma skin cancer in transplant recipients. The benefit was most pronounced in patients who converted from an established immunosuppressive regimen to sirolimus. Given the risk of mortality, however, the use of this drug does not seem warranted for most patients with kidney transplant. Further research is needed to determine if different populations, such as those at high risk of cancer, might benefit from sirolimus.

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.

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.

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.

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.