2,8-Dihydroxyadenine Nephropathy Identified as Cause of End-Stage Renal Disease After Renal Transplant.

Adenine phosphoribosyltransferase deficiency is a rare autosomal recessive disorder of uric acid metabolism that leads to formation and excretion of 2,8-dihydroxyadenine into urine. The low solubility of 2,8-dihydroxyadenine results in precipitation and formation of urinary crystals and renal stones. Patients with this disorder usually have recurrent nephrolithiasis and can develop nephropathy secondary to crystal precipitation in the renal parenchyma. The disease is most often underdiagnosed and can recur in renal transplant, causing graft failure. Lack of specific clinical manifestations, chemical and radiologic features identical to those shown with uric acid stones, and lack of awareness among clinicians are among the causes for the underdiagnoses of this treatable disease. Allopurinol, a xanthine dehydrogenase inhibitor, is the mainstay of treatment, supported by high fluid intake and dietary modifications. The possibility of adenine phosphoribosyl transferase deficiency should be considered in all cases of urolithiasis in children, patients with recurrent urolithiasis, and patients with urolithiasis associated with renal failure of unknown cause, including patients with end-stage renal disease and renal transplant recipients. Here, we report a case of a 41-year-old female patient who had a late diagnosis of 2,8-dihydroxyadenine nephropathy-induced end-stage renal disease, made on the native nephrectomy that accompanied the renal transplant, and who had a timely intervention that prevented recurrence in the graft.

Long-acting erythropoietin stimulating agents for persistent anemia after kidney transplant: risk factors and outcome.

OBJECTIVES: Posttransplant anemia is associated with an increased risk of congestive heart failure, left ventricular hypertrophy, and death. The purpose of this study was to evaluate the effect of long-acting erythropoietin-stimulating agents on anemia after kidney transplant. MATERIALS AND METHODS: In 2306 kidney transplant recipients, 250 anemic patients (11%) with stable graft function were followed at the Hamed Al-Essa Organ Transplant Centre (Kuwait) and were assessed for anemia. We enrolled 120 patients into this open-label study in 2 groups: group 1 had treatment with darbepoetin alfa (86 patients) and group 2 had continuous erythropoietin receptor activator (34 patients). RESULTS: Patient age correlated negatively with serum iron level. Serum ferritin correlated negatively with hemoglobin level 6 months after transplant but not at time of transplant. Most patients were women who received their grafts from male donors. The 2 groups were comparable in frequency of rejection and mean hemoglobin and serum albumin levels at 3, 6, 9, and 12 months after transplant. There was no difference between the 2 groups in renal function (estimated glomerular filtration rate); posttransplant complications such as new-onset diabetes after transplant, hypertension, serious bacterial infections, or patient and graft outcomes. CONCLUSIONS: Anemia is an important problem after kidney transplant, and iron use is suboptimal in kidney transplant recipients. Darbepoetin alfa and continuous erythropoietin receptor activator had comparable positive results.

Successful management of critical illness polyneuropathy and myopathy in renal transplant recipients.

Critical illness polyneuropathy and myopathy commonly occur in patients with multiorgan failure and sepsis. Distal muscle weakness and loss of deep tendon reflexes are usually found, with sparing of the cranial nerve musculature. Many risk factors have been identified, specifically hypoxia, hypotension, hyperpyrexia, and age. Other independent risk factors include female sex, severity of illness, duration of organ dysfunction, renal failure and renal replacement therapy, hyperosmolality, parenteral nutrition, low serum albumin level, duration of intensive care unit stay, vasopressor and catecholamine support, and central neurologic failure. Hyperglycemia also has been identified as an independent risk factor, with important potential affect in terms of prevention. Herein, we report the development of critical illness polyneuropathy and myopathy in 7 of 22 renal transplant recipients who underwent successful ventilator weaning during treatment for bronchopneumonia. This is the first report of critical illness polyneuropathy and myopathy among renal transplant recipients. Clinical suspicion and electrophysiologic studies are tools for early diagnosis. Proper management, including correction of risk factors (especially diabetes) and long-term rehabilitation measures might be beneficial.

Detection and monitoring of cytomegalovirus infection in renal transplant patients by quantitative real-time PCR.

OBJECTIVES: To establish a sensitive and specific real-time PCR for quantitation of cytomegalovirus (CMV) DNA in clinical specimens. SUBJECTS AND METHODS: In a prospective study, CMV DNA was quantified in blood samples of 255 kidney recipients with and without CMV-related symptoms between the years 2000 and 2005 in Kuwait. In a selected group of patients, the effect of anti-CMV chemotherapy was monitored by quantitative real-time PCR (qRT-PCR). RESULTS: The established qRT-PCR assay had a sensitivity to detect 30 CMV DNA copies. CMV DNA was detected in 54/255 (24%) patients; of these, 17 (31.5%) were asymptomatic, and 37 patients (68.5%) had symptomatic CMV infection. Sequential blood specimens were collected from all CMV-positive patients and tested by CMV pp65 antigenemia and qRT-PCR assays. There was a moderate positive correlation between the two assays (Pearson's correlation = 0.52). The median CMV viral load measured by qRT-PCR was higher in symptomatic (6.5 x 10(4) copies/ml) than in asymptomatic (185copies/ml) patients (p = 0.001). The estimated cut-off value of CMV DNA for CMV symptoms/disease was > or =800 copies/ml of blood. Testing of sequential samples from patients treated with symptomatic CMV infection showed that the viral load was significantly reduced after 3 weeks of anti-CMV chemotherapy (p = 0.001). CONCLUSION: The reported qRT-PCR is a sensitive method for quantitation of CMV DNA in the blood of kidney recipients and can be useful in monitoring the efficacy of anti-CMV therapy.

Inferior long-term outcome of renal transplantation in patients with diabetes mellitus.

OBJECTIVE: To retrospectively review the long-term outcome of renal transplant in diabetics at Mubarak Al-Kabeer Hospital and Hamad Al-Essa Organ Transplant Center, Kuwait from 1983 to 1998. METHODS: There were 631 renal transplant patients, comprising 79 (12.5%) patients with pretransplant diabetes mellitus (pre-TDM), 117 (18.5%) patients with post-transplant diabetes mellitus and 435 (69%) nondiabetics (ND). Subjects with post-transplant diabetes mellitus were excluded from the comparative analysis. Distribution of sex, source of donors and mode of immunosuppression were similar in pre-TDM and ND groups. RESULTS: Fifty-three (67%) recipients in pre-TDM and 90 (20.5%) in the ND group (p < 0.01) were above 45 years of age. However, 26 (33.3%) pre-TDM and 345 (79.5%) ND were below age 45. Among those who died, coronary artery disease led to death in 36% of pre-TDM and 27% in ND. Hyperlipidemia requiring drug therapy was observed in 37% pre-TDM and 6% ND. The incidence of severe infections was nearly twice in pre-TDM over ND recipients (1.9 vs. 1.0 per patient, p < 0.001). Acute rejection episodes were more frequently seen in pre-TDM (43%) than ND (33%), however the difference was not statistically significant. The patient survivals at 1, 5, 10, 14 years were significantly lower in pre-TDM (84, 65, 58 and 58%, respectively) than in ND (97, 93, 86 and 82%, respectively). The major contributory factors were severe infections and coronary artery disease. The cumulative graft survival showed a similar pattern (52% in pre-TDM, 73% in ND at 10 years). However, when death is excluded, the 10-year pure graft survival probability was similar for the pre-TDM and ND groups (76% vs. 80%). CONCLUSION: Our study indicates poor patient survival in pre-TDM due to coronary artery disease and infections, whereas the pure long-term graft survival was equally good in pre-TDM and ND transplant recipients.