[Denosumab and fracture risk in kidney transplant].

Background: Kidney transplant patients bear a higher risk of bone disease. The monoclonal antibody Denosumab (Den), by binding RANKL, reduces osteoclastic activity and increases mineral density (BMD), thus limiting the risk of bone fractures. We evaluated the efficacy and safety of Den in kidney transplant patients who developed bone fractures. Methods: Thirteen kidney transplant recipients (aged from 50 to 79 years 7M and 6F, with an average 9,9 years follow up after transplantation, and nearly normal renal function (GFR 62±15 ml/min/1.73m2), who developed low-energy vertebral fractures (21 dorsal and 1 lumbar) after transplantation, had been evaluated for 2 years with Dual-energy X-ray absorptiometry (DEXA) and morphometric absorptiometry (MXA) while receiving Den (four 60-mg doses). Data for vertebral heights and posterior-anterior height ratios (P/A), and BMD values for vertebral, femoral, and radius were obtained. The immunosuppressive regimen consisted of CNI and MMF, and 8 out of 13 were taking prednisone. A fixed dose of 450.000 UI-year of cholecalciferol was prescribed to all patients. Whole-PTH, 25-OHD3, and alkaline phosphatase (ALP) were also evaluated. Results: After 2 years of Den treatment, we observed a significative increase in vertebral T-score (from -2.12±0.35 to -1.67±0.35; p < 0.02), while T score of femoral neck and radius did not show significative variation (-1.86±0.21 versus -1.84±0.23 and -3.04±0.42 versus -3.19±0.45, respectively). We found a lower incidence of fracture/patient-year pre and post Den 0.17 [95 CI 0.11-0.24] vs 0.07 [95% CI 0.02-0.3] respectively. No significative variations were observed in whole-PTH (89.31±19.9 pg/ml versus 68.38±9.8 pg/ml), 25OHD3 (24.02±2.75ug/L versus 26.67±2.29 ug/L) and alkaline phosphatase (78.46±12.73UI/L versus 56.77±7.14UI/L). No adverse events were registered. Conclusions: Treatment with Den improve BMD in vertebral bone and possibly reduces the risk of low-energy vertebral fractures in kidney transplant patients.

Prevalence and clinical correlates of hyperkalemia in stable kidney transplant recipients.

Although hyperkalemia (HK) is often associated with adverse clinical outcomes in renal patients, few studies are available in the setting of kidney transplantation. Therefore, we evaluated prevalence and clinical correlates of HK in stable kidney transplant recipients (KTRs) on standard of care immunosuppressive therapy. We studied 160 stable KTRs (post-transplant vintage 46.6 ± 16.6 months), most of whom (96.2%) on calcineurin inhibitor (CNI)-based immunosuppressive therapy. HK was defined as plasma potassium levels above 5 mEq/L, confirmed in two consecutive samples. Office blood pressure was measured, and renal graft function was expressed by estimated glomerular filtration rate (eGFR), calculated according to the CKD-EPI formula. HK prevalence was 8.8%, and plasma K above 5.5 mEq/L was found in 2.5% of all KTRs. In the univariate logistic regression analysis HK was significantly associated with serum urea concentration (OR 1.03, 95% CI 1.01-1.05 for each 1 mg/dL increase), tCO2 (OR 0.77, 95% CI 0.66-0.90 for each 1 mmol/L increase), the presence of arterial hypertension (OR 4.01, 95% CI 1.3-12.64), the use of RAAS inhibitors (OR 5.26, 95% CI 1.6-17.7), and eGFR less than 30 ml/min/1.73 m2 (OR 7.51, 95% CI 2.37-23.77). By multivariable backward stepwise regression analysis, the presence of metabolic acidosis (OR 0.83, 95% CI 0.69-0.99, P = 0.04), arterial hypertension (OR 4.65 95% CI 1.01-17.46 P = 0.03), and to be administered RAAS inhibitors (OR 6.11, 95% CI 1.03-25.96 P = 0.03) remained significantly associated with HK. We conclude that in stable KTRs the prevalence of HK is about 9%, slightly lower than previously reported. Moreover, it is not associated with eGFR, but with metabolic acidosis, arterial hypertension, and the use of RAAS inhibitors.

De novo post-transplant thrombotic microangiopathy localized only to the graft in autosomal dominant polycystic kidney disease with thrombophilia.

INTRODUCTION: Thrombotic microangiopathy (TMA) is a serious complication of renal transplantation and is mostly related to the prothrombotic effect of calcineurin inhibitors (CNIs). A subset of TMA (29%-38%) is localized only to the graft. Case 1: A young woman suffering from autosomal dominant polycystic kidney disease (ADPKD) underwent kidney transplant. After 2 months, she showed slow renal deterioration (serum creatinine from 1.9 to 3.1 mg/dl), without hematological signs of hemolytic-uremic syndrome (HUS); only LDH enzyme transient increase was detected. Renal biopsy showed TMA: temporary withdraw of tacrolimus and plasmapheresis was performed. The renal function recovered (serum creatinine 1.9 mg/dl). From screening for thrombophilia, we found a mutation of the Leiden factor V gene. Case 2: A man affected by ADPKD underwent kidney transplantation, with delay graft function; first biopsy showed acute tubular necrosis, but a second biopsy revealed TMA, while no altered hematological parameters of HUS was detected. We observed only a slight increase of lactate dehydrogenase (LDH) levels. The tacrolimus was halved and plasmapheresis was performed: LDH levels normalized within 10 days and renal function improved (serum creatinine from 9 to 2.9 mg/dl). We found a mutation of the prothrombin gene. Only a renal biopsy clarifies the diagnosis of TMA, but it is necessary to pay attention to light increasing level of LDH. CONCLUSION: Prothrombotic effect of CNIs and mTOR inhibitor, mutation of genes encoding factor H or I, anticardiolipin antibodies, vascular rejection, cytomegalovirus infection are proposed to trigger TMA; we detected mutations of factor II and Leiden factor V, as facilitating conditions for TMA in patients affected by ADPKD.

Post-infectious glomerulonephritis presenting as acute renal failure in a patient with Lyme disease.

INTRODUCTION: We report a case of a patient with acute renal failure in Lyme disease-associated focal proliferative mesangial nephropathy. Lyme disease is a vector-borne disease caused by Borrelia burgdorferi, transmitted by the bite of an infected ixodes tick. Post-infectious glomerulonephritis (GN)secondary to Borrelia burgdorferi infection in man could be fatal, as it is in canine Lyme borreliosis. CASE: A 61-year old man with chronic ethanolic hepatitis was admitted to a provincial hospital, complaining of nausea, diarrhoea and loss of his sense of taste. A few days prior hospitalization, he had been bitten by a tick. He developed erythema gyratum repens in the right leg, thorax and face. Kidney function was altered despite normal urine flow: creatinine 5.04 mg/dl and BUN 126 mg/dl. Urinalysis showed light proteinuria and microscopic hematuria. IgG and IgM antibodies to Borrelia burgdorferi were detected by ELISA and Western blot confirmed the diagnosis. Renal biopsy showed mild mesangial proliferation and mesangial and paramesangial deposits on AFOG stain. A diagnosis of acute renal failure in Lyme disease-associated focal proliferative IgA nephropathy was made. Intravenous antibiotic medication was started (ceftriaxone 1 gram daily i.v.). The patient was later discharged, serum creatinine had decreased to 3.5 mg/dl with a BUN of 58 mg/dl, and a slight improvement was observed on follow-up. CONCLUSION: Borrelia burgdorferi is a possible cause of post-infectious GN in humans as it is in dogs. Difficulties in identifying Borrelia burgdorferi may also be one of the reasons for the paucity of reports on the association of this infection with glomerulonephritis in humans. Currently, various types of histological renal lesions have been reported.