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Background: Persistent hyperparathyroidism is one of the main causes of hypercalcemia following kidney transplantation; differential diagnosis is required., Case Presentation: We report the case of a 61-year-old kidney transplant recipient who underwent transplant in September 2016. She was admitted in March 2017 presenting with a 3-week history of asthenia, hypotension, and cough. Laboratory analysis showed acute kidney injury with hypercalcemia and elevation of inflammatory markers. She was initially treated with hydration therapy. A few days after admission she developed respiratory failure: chest computed tomography showed a ground-glass pattern. A diagnosis of Pneumocystis jirovecii was made on bronchoalveolar lavage. A subsequent graft biopsy was performed that revealed intratubular calcium deposition without signs of rejection. The patient was given trimethoprim/sulfamethoxazole, with improvement in pulmonary and renal function as well as improvement in hypercalcemia., Conclusions: P jirovecii infection can trigger activation of intra-alveolar macrophages that leads to extrarenal vitamin D production with subsequent hypercalcemia. This rare event should be considered in renal transplant patients with pulmonary infection accompanied by hypercalcemia. In our case, hypercalcemia also provoked acute kidney injury., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Recurrence of focal segmental glomerulosclerosis (FSGS) in renal allograft recipients after first transplant occurs in the second graft in virtually all patients. There is little evidence regarding optimal treatment., Case Presentation: A 55-year-old man with primary FSGS and disease recurrence in both the first and the second kidney grafts is presented. In 1999, the patient developed FSGS 3 years after transplant, which was treated with plasmapheresis and cyclophosphamide. Hemodialysis was started at 8 years from the onset of relapse. In February 2014, the patient received a second kidney transplant, and after 2 weeks laboratory analysis showed nephrotic proteinuria (5.9 g/d) with increased serum creatinine. Biopsy results revealed recurrence of FSGS. At that time, he was treated with steroids and plasmapheresis with partial efficacy, achieving a serum creatinine level of 1.1 mg/dL with decreased proteinuria (1 g/d). After 4 months, creatinine worsened (1.6 mg/dL) with new evidence of proteinuria. Second biopsy results showed evidence of FSGS progression. The patient then received plasmapheresis and 2 doses of rituximab. Follow-up was characterized by progressive remission up to complete resolution. The patient is currently free from relapses after 3 years with good renal function and almost no proteinuria., Conclusions: More evidence and prospective studies are needed to better understand the role of rituximab in FSGS in order to obtain an optimized therapeutic protocol for recurrence of FSGS in renal transplant recipients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Kidney transplantation is a life-saving treatment for patients with end-stage renal disease. However, despite progress in surgical techniques and patient management, immunological rejection continues to have a negative impact on graft function and overall survival. Incompatibility between donors and recipients for human leukocyte antigens (HLA) of the major histocompatibility complex (MHC) generates a series of complex cellular and humoral immune response mechanisms that are largely responsible for rejection and loss of graft function. Within this context, a growing amount of evidence shows that alloreactive natural killer (NK) cells play a critical role in the immune response mechanisms elicited by the allograft. Killer immunoglobulin-like receptors (KIRs) are prominent mediators of NK cell alloreactivity., Methods and Findings: A cohort of 174 first cadaveric kidney allograft recipients and their donors were selected from a total cohort of 657 transplanted patients for retrospective immunogenetic analyses. Patients with HLA Class II mismatches were excluded. HLA Class I allele frequencies were compared among patients with chronic rejection, patients with stable graft function and a group of 2388 healthy controls. Activating and inhibitory KIR gene frequencies, KIR haplotypes, KIR-HLA ligand matches/mismatches and combinations of recipient KIRs and donor HLA Class I ligands were compared among patients with and without chronic rejection and a group of 221 healthy controls. Patients transplanted from donors homozygous for HLA-C1 antigens had a significantly higher risk for chronic rejection than patients transplanted from donors homozygous or heterozygous for HLA-C2 antigens or with epitopes belonging to the HLA-Bw4 ligand group. The Kaplan-Meier curves obtained by dividing the patients into 3 groups according to the presence or absence of one or both of the combinations of recipient KIRs and donor HLA ligands (rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4) showed a significantly higher cumulative incidence of chronic rejection in the group of patients completely lacking these functional units. These patients showed a progressively stronger decline in modification of diet in renal disease-estimated glomerular filtration rate., Conclusions: KIR genotyping should be performed at the time of enrolment of patients on the waiting list for organ transplantation. In our study, a significantly higher risk of chronic rejection after kidney transplantation was observed when recipient (r) and donor (d) pairs completely lacked the two functional rKIR-dHLA ligand combinations rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4. This immunogenetic profile corresponds to low levels of NK cell inhibition. Therefore, patients with this high risk profile could benefit from immunosuppressive therapy aimed at reducing NK-cell cytotoxicity.

Background: Both the membrane-bound and soluble forms of human leukocyte antigen-G (HLA-G) molecules exhibit a multitude of immunomodulatory properties that can potentially obviate or delay graft rejection. The 14-base pair (14-bp) polymorphism in the 3'-untranslated region of the HLA-G gene is thought to have a role in soluble HLA-G (sHLA-G) expression., Methods: In this study, we retrospectively investigated a large cohort of 418 kidney transplant recipients with the aim of establishing whether the HLA-G 14-bp insertion/deletion polymorphism could serve as an effective genetic risk marker for acute and/or chronic deterioration of transplanted kidney function., Results: A statistically significant higher incidence of chronic kidney dysfunction leading to allograft loss was observed in transplant recipients homozygous for the HLA-G 14-bp deletion polymorphism. This difference increased over time and was confirmed by progressive decline in the glomerular filtration rate., Conclusions: These results suggest that alongside other factors previously consolidated in clinical practice, recipient HLA-G 14-bp genotype may serve as an adjuvant independent predictor of long-term outcome of kidney transplantation.

Dialysis treatments have allowed 'terminal patients' to live for years and years. However, life expectancy and quality are still consistently reduced in renal dialysis patients. Consequently, all efforts to device alternative treatments to the conventional ones are highly justified. Recently, the Hemo Study showed that neither the use of high flux membranes, nor the increase of the dialysis dose above the conventional, were capable to reduce significantly patient's mortality and morbidity, although 8% reduction of the risk of death was seen in patients treated with high flux vs. patients treated with low-flux dialysis. A relevant question is if convective treatments may offer an overprotection from morbidity and mortality, in comparison with low flux and high flux treatments. Data from the Registro Lombardo di Nefrologia e Trapianto published in 2000 showed a trend toward a better survival (RR= 90) and a significantly better protection from tunnel carpal syndrome (RR= 0.58; p= 0.03) in patients treated with convective treatments (hemofiltration and/or hemodiafiltration) vs. patients treated with diffusive dialysis. Except than a better cardiovascular stability observed on hemofiltration and an higher beta2-microglobuline clearance given by online hemofiltration and hemodiafiltration, evident clinical benefits of convective treatments, over the conventional high flux treatments, are not yet clearly demonstrated. Notwithstanding that, online convective treatments, that are performed with high flux compatible membranes and high technology machines, producing high quality water, offer at the moment the best bases for the improvement of clinical results of dialysis, especially in some category of patients.