New-Onset Diabetes as a Complication After Kidney Transplant: Incidence and Outcomes.

OBJECTIVES: Diabetes after kidney transplant is a common complication. It may increase the risk of cardiovascular disease and mortality after kidney transplant. The aim of this study was to examine the effects of diabetes that developed after transplant on outcomes in kidney transplant recipients. MATERIALS AND METHODS: This study included renal allograft recipients without diabetes who received transplants from 2008 to 2019 in our Department of Nephrology at Sahloul Hospital (Tunisia). Demographic and clinical data at transplant time and clinical events during the study period were collected. Patient and graft survival rates were analyzed. Patients with and without diabetes after transplant were compared. RESULTS: In the 257 patients (median age of 36 years) included in our study, the overall incidence of diabetes after transplant was 21.8%. Laboratory data (serum cholesterol, serum creatinine at discharge, and 24-hour proteinuria) were similar in those with and without diabetes after transplant. We observed no significant differences in cardiovascular diseases and infectious complication rates between patients with and without diabetes after transplant. There was also no significant difference in graft loss at 5 years between those with and without diabetes after transplant (P = .582). The 5-year patient survival rate in kidney transplant recipients with diabetes after transplant was 87.5%. There was no significant difference in death rate between those with and without diabetes after transplant (P = .566). CONCLUSIONS: Diabetes after transplant affected graft and patient survival and increased the incidence of posttransplant cardiovascular disease. The incidence and impact of diabetes after transplant can be minimized through pre- and posttransplant screening to identify patients at higher risk.

BK and JC polyomavirus infections in Tunisian renal transplant recipients.

The aim of this prospective study was to investigate the rate of BK (BKPyV) and JC (JCPyV) polyomavirus infections and their influence on allograft function in Tunisian renal transplant recipients. A total of 72 renal transplant recipients were studied. BKPyV and JCPyV were detected and quantified by real-time PCR in urine and plasma. Demographic and laboratory characteristics were collected for each patient. Polyomavirus DNAuria was detected in 54 (75%) of renal transplant recipients: 26 (36%) had BKPyV DNAuria, 20 (28%) had JCPyV DNAuria, and 8 (11%) had a dual BKPyV/JCPyV DNAuria. BKPyV DNAemia was detected in four (5.5%) patients, whereas no patient had JCPyV viremia. More than 70% of BKPyV and JCPyV infections started within the first 3 months post-transplant. The risk for positive DNAemia was observed in patients with DNAuria level >10(7) copies/ml. BK Polyomavirus-associated nephropathy (BKPyVAN) was observed in two patients. This study highlights the high frequency of BKPyV and JCPyV viruria during the first year post-transplant with the highest incidence observed in the third month. We identified several risk factors that were associated with BKV DNAuria including age, sex of patients, and the use of tacrolimus instead of cyclosporine A at month 3. The use of cyclosporine A instead of tacrolimus was identified as risk factor for JCV viruria in month 3. No statistical difference in the allograft function was found between BKPyV and/or JCPyV infected and uninfected patients.

Role of recombinant human erythropoietin in mitomycin C-induced genotoxicity: analysis of DNA fragmentation, chromosome aberrations and micronuclei in rat bone-marrow cells.

Mitomycin C (MMC) is one of the most effective chemotherapeutic agents. However, during clinical use several side effects may occur. Recombinant human erythropoietin (rhEPO), a glycoprotein that regulates haematopoiesis, has been shown to exert an important cyto-protective effect in many tissues. The aim of this study was to explore whether rhEPO protects against MMC-induced genotoxicity in rat bone-marrow cells. Adult male Wistar rats were divided into six groups of 18 animals each: a control group, a 'rhEPO alone' group, an 'MMC alone' group and three 'rhEPO+MMC' groups (pre-, co- and post-treatment conditions). Our results show that MMC induced a noticeable genotoxic effect in rat bone-marrow cells. rhEPO reduced the effects of MMC significantly in every type of experiment conducted, such as the frequency of micronuclei, the percentage of chromosome aberrations and the level of DNA damage measured with the comet assay. The protective effect of rhEPO was more efficient when it was given 24h prior to MMC treatment.

Distribution of JC polyomavirus genotypes in Tunisian renal transplant recipients between January 2008 and January 2011.

The polyomavirus JC (JCPyV) is a ubiquitous virus in humans, causing progressive multifocal leukoencephalopathy, a fatal demyelinating disease. JCPyV propagates in the adult kidney and excretes its progeny in urine, from which its DNA can be recovered readily. JCPyV isolates worldwide can be classified into 14 subtypes or genotypes, each associated with a specific geographical region. The European genotypes EU-a-b-c are spread throughout Europe and Mediterranean areas. The major African genotype Af2 is spread not only throughout Africa but also in West and South Asia. A minor African genotype (Af1) occurs in Central and West Africa. Partially overlapping domains in Asia were occupied by various genotypes (e.g., B1-a, -b, -d, B2, CY, MY, and SC). To characterize the subtypes of JCPyV prevalent in Tunisia, the presence of the virus was investigated by real-time PCR in urine samples from 98 renal transplant recipients. For subtype identification, a 610 bp typing region of the JCPyV genome was amplified from each urine sample, and its DNA sequence was determined. In the patients studied, the major African subtype Af2 was the predominant (62.5%), followed by the European subtype EU (33.5%). Only one case clustering with the Asian genotype SC (4%) was identified. The presence of the European subtype with high prevalence in this population suggests that the epidemiological distribution of JCPyV virus sequences in North Africa is related partially to the epidemiological data in Europe.

Induction of DNA fragmentation, chromosome aberrations and micronuclei by cisplatin in rat bone-marrow cells: protective effect of recombinant human erythropoietin.

Cisplatin (Cisp) is one of the most effective chemotherapeutic agents. However, at higher doses several side effects may occur. Recombinant human erythropoietin (rhEPO), a glycoprotein regulating haematopoiesis, has recently been shown to exert an important cyto-protective effects in many tissues. The purpose of this study was to explore whether rhEPO protects against Cisp-induced genotoxicity in rat bone-marrow cells. Adult male Wistar rats were divided into six groups of 18 animals each: control group, rhEPO-alone group, Cisp-alone group and three rhEPO+Cisp-groups (pre-, co- and post-treatment condition, respectively). Our results show that Cisp induced a noticeable genotoxic effect in rat bone-marrow cells. In all types of treatment, rhEPO significantly decreased the frequency of micronuclei, the percentage of chromosome aberrations and the level of DNA damage. The protective effect of rhEPO was more efficient when it was administrated 24h before exposure to Cisp.

Recombinant human erythropoietin prevents cisplatin-induced genotoxicity in rat liver and heart tissues via an antioxidant process.

Cisplatin (Cisp) is one of the most effective chemotherapeutic agents. However, at higher doses, liver and heart injuries may occur. Recombinant human erythropoietin (rhEPO) has recently been shown to exert an important cytoprotective effect in many tissues. For that reason, we tried to check the protective effect of rhEPO against Cisp-induced genotoxicity and oxidative stress in liver and heart tissues. Our experiments were performed using six groups of adult male Wistar rats. The control group was treated only with saline solution. The rhEPO group was given a single dose of rhEPO. The Cisp group was given a single injection of Cisp. The rhEPO+Cisp groups were given rhEPO simultaneously, 24 hours before, and 5 days after Cisp injection. Our results clearly showed that Cisp induced noticeable DNA damage in the liver and heart, accompanied by a significant increase in protein carbonyl level, reduced glutathione (GSH) depletion, and a decrease in catalase activity. Rats treated with rhEPO, simultaneously, before, or after Cisp injection, remarkably decreased DNA damage. It decreased also the protein carbonyl level, restored GSH depletion, and enhanced catalase activity. Our results highlight an interesting cytoprotective strategy using rhEPO against Cisp-induced liver and heart injuries.

Protective effect of erythropoietin against cisplatin-induced nephrotoxicity in rats: antigenotoxic and antiapoptotic effect.

Cisplatin (Cisp) is an active cytotoxic agent that was found efficient in the treatment of various types of solid tumors. Its nephrotoxic effect has been very well documented in clinical oncology. Erythropoietin (EPO), a renal cytokine-regulating hematopoiesis, has recently been shown to exert important cytoprotective effects in many experimental injuries. The aim of this study was to explore whether EPO would protect against Cisp-induced apoptosis in rat kidney. Adult Wistar rats were treated with saline solution as the control group, Cisp alone, EPO alone, or EPO with Cisp in different treatments: 1) EPO and Cisp simultaneously administrated to animals as a cotreatment; 2) EPO administered 24 hours before Cisp as a pretreatment; and 3) EPO administered 5 days after Cisp injection as a post-treatment. Our results have shown that Cisp induced renal failure, characterized with a significant increase in serum creatinine and blood urea nitrogen (BUN) concentrations. Cisp promoted kidney DNA fragmentation and apoptotic cell death. Apoptosis was revealed by an enhancement of proapoptotic protein (e.g., p53 and Bax) levels, decrease in antiapoptotic proteins (e.g., Bcl2 and Hsp27), and increase in caspase-3 activity. Treatments with EPO restored creatinine and BUN levels and inhibited Cisp-induced DNA damage in the kidney. Apoptosis was also reduced by the upregulation of antiapoptotic protein expressions, downregulation of proapoptotic protein levels, and reduction of caspase-3 activity.

Protective effect of recombinant human erythropoietin against cisplatin-induced oxidative stress and nephrotoxicity in rat kidney.

Cisplatin (Cisp) is one of the most widely used chemotherapeutic agents for the treatment of several human malignancies. The efficacy of Cisp is dose dependent and at higher doses serious kidney injury may occur. Recombinant human erythropoietin (rhEPO) has recently been shown to exert an important cytoprotective effect in experimental brain injury and ischemic acute renal failure. The aim of the present study was to explore whether rhEPO administration is protective against Cisp-induced oxidative damage and renal injury. Our results showed that Cisp induced a marked oxidative stress and renal failure. Administration of rhEPO (pre-, co- or postadministration with regard to Cisp) decreased oxidative damage induced by Cisp. Recombinant human EPO reduced malondialdehyde and protein carbonyl levels. Recombinant human EPO also prevented glutathione depletion and ameliorated the increased catalase activity induced by Cisp treatment. Furthermore, rhEPO restored creatinine and blood urea nitrogen levels increased by Cisp. We concluded that rhEPO administration especially in pretreatment condition protected rats against Cisp-induced renal oxidative stress and nephrotoxicity.

Distribution of BK polyomavirus genotypes in Tunisian renal transplant recipients.

BK polyomavirus (BKV) is a ubiquitous virus in humans that remains latent in the urogenital tract after a primary infection during childhood. The virus, which is reactivated frequently and excreted in urine, can cause nephropathy in renal transplant recipients. BKV sequences are classified into four subtypes (I-IV). Subtype I and IV are divided further into four and six subgroups, respectively. To characterize the subtypes of BKV prevalent in Tunisia, the presence of the virus was investigated by real-time PCR in urine samples from 77 renal transplant recipients. For subtype identification, a DNA fragment in the VP1 coding region, amplified by nested PCR from positive samples, was sequenced and a phylogenetic analysis was performed. In the studied population, subtype I (75.5%), II (14.5%), and IV (2.5%) were identified with a clear predominance of subtype Ib-2 (73%) as observed in European population. This study suggests that in North Africa, the BKV genotype distribution is similar to that of Europe and different from that of sub-Saharan Africa.