End-proximal tubule phosphate concentration increases as GFR falls in humans: measurement by means of a lithium clearance-based methodology.

BACKGROUND: Microscopic nephrocalcinosis secondary to intratubular calcium phosphate (CaP) precipitation is thought to accelerate progression to end-stage renal failure in chronic kidney diseases. In phosphorus (P)-loaded uninephrectomized rats, intratubular CaP crystal formation and progressive tubular damage occurred when end-proximal tubule P concentration (ePTpc) increased above a threshold level. METHODS: We have calculated ePTpc in humans by urine P and creatinine concentration, with the end-proximal tubule fluid volume calculated either as lithium (Li) clearance (ePTpc-Li) or as a fixed 0.7 fraction of glomerular filtration rate (GFR), as published (ePTpc-70). Healthy people undergoing living transplant kidney donation before (DON-pre, n = 70) and after (DON-post, n = 64) nephrectomy and 25 patients with stage 2-5 CKD were investigated while on regular free diet. RESULTS: ePTpc showed a stepwise increase with decreasing functional renal mass (DON-pre 2.51 ± 0.99 and 1.56 ± 0.47 mg/dL for ePTpc-Li and -70 calculation, respectively; DON-post 3.43 ± 1.14 and 2.18 ± 0.44;  CKD 5.68 ± 3.30 and 3.00 ± 1.30, P < .001 for all); ePTpc was inversely correlated with Ccr and directly with PTH, fractional P excretion and excretion (UpV) corrected for GFR (P < .001 for all), but not with Pp. ePTpc-Li and ePTpc-70 were significantly correlated (r = 0.62, P < .001), but ePTpc-70 was lower than the corresponding ePTpc-Li. Levels of ePTpc increased above a suggested dangerous threshold when daily UpV/GFR was higher than about 10 mg/mLCcr. CONCLUSIONS: ePTpc progressively increases in humans as functional renal mass falls independently from plasma P levels. Main determinants of ePTpc rise are GFR fall, degree of phosphaturia per unit GFR and P intake corrected for GFR. It may become a novel, potentially useful, indicator to guide management of CKD patients.

An enigmatic case of IgG4-related nephropathy and an updated review of the literature.

IgG4-related disease (IgG4-RD) is still an underestimated disorder which affects multiple organs, and its recognition as a distinct clinical disease has been only proved in the recent decades. The renal involvement has been documented in approximately 15% of patients with IgG4-RD, and the typical manifestation is a tubulo-interstitial nephritis. The main histological findings in IgG4-RD are typically a dense tissue infiltration of IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis, and frequently elevated IgG4 serum levels. Herein we report our atypical and peculiar clinical presentation of an IgG4-related nephropathy (IgG4-RN) and the remarkable response to rituximab (RTX) treatment at the renal imaging with computerized tomography assessment. The current nephrological evidences support the renal function recovery after steroids or steroids plus RTX therapy, even if the renal imaging data are not always shown. In a complex and enigmatic clinical scenario such as the IgG4-RN, both the renal biopsy and the renal imaging before and after the immunosuppressive therapy become mandatory tools to thoroughly define the diagnosis, the management and the response to the immunological therapy.

Single Session and Weekly Beta 2-Microglobulin Removal with Different Dialytic Procedures: Comparison between High-Flux Standard Bicarbonate Hemodialysis, Post-Dilution Hemodiafiltration, Short Frequent Hemodialysis with NxStage Technology and Automated Peritoneal Dialysis.

BACKGROUND: NxStage System One cycler (NSO) is a widespread system for home daily dialysis. Few data are available on the impact of this "low dialysate volumes system" on the removal rate of poorly diffusible, time-dependent solutes like ß2-microglobulin (ß2M). METHODS: Single-session and weekly balances of ß2M were performed and compared in 12 patients on daily NSO, 13 patients on standard high-flux bicarbonate dialysis (BHD), 5 patients on standard post-dilution on line hemodiafiltration (HDF), and 13 patients on automated peritoneal dialysis (APD). RESULTS: Intradialytic fall of plasma water ß2M levels (corrected for rebound) was 65.2 ± 2.6% in HDF, 49.8 ± 9.1% in BHD, and 32.3 ± 6.4% in NSO (p < 0.001 between all groups). Single treatment dialysate removal was much less in APD (19.4 ± 20.4 mg, p < 0.001) than in any extracorporeal technologies, and was less in NSO (126.2 ± 35.6 mg, p < 0.001) than in BHD (204.9 ± 53.4 mg) and HDF (181.9 ± 37.6 mg), with no differences between the latter 2; however weekly removal was higher in NSO (757.3 ± 213.7 mg, p < 0.04) than in BHD (614.8 ± 160.3 mg) and HDF (545.8 ± 112.8 mg). Extrapolated ß2M adsorption to the membrane was negligible in BHD, 14.7 ± 9.5% of total removal in HDF and 18.3 ± 18.5% in NSO. Integration of single session data into a weekly efficiency indicator (K × t) showed total volume of plasma cleared in NSO (33.4 ± 7.7 L/week) to be higher than in BHD (26.9 ± 7.2 L/week, p < 0.01) and not different than in HDF (36.2 ± 4.7 L/week); it was negligible (3.2 ± 1.0) in APD. CONCLUSIONS: Weekly ß2M removal efficiency proved equal and highest in HDF and NSO (at a 6/week prescription), slightly lesser in BHD and lowest in APD.

[Immunosuppression in kidney transplantation: a way between efficacy and toxicity].

Renal transplantation is the best treatment for patients with end-stage renal disease. Over the last decades, the introduction of new immunosuppressive agents resulted into the reduction of the incidence of acute rejection and early graft loss. Despite this progress, there has been little improvement in the average life of the transplant. The main reasons of late failure are patient's death due to several complications (e.g. cancer, infectious or metabolic), and progressive deterioration of renal function caused by immunological and non-immunological factors. The immunosuppressive therapy can be distinguished into two components: the induction therapy and the maintenance therapy. The former has the aim to implement intense and immediate immunosuppression. This therapy is mostly useful in transplant with high immunological risk, although it is correlated with an increased risk of cytopenias and viral infections. The latter offers the rationale to prevent organ rejection and minimize drug toxicity. This is generally constituted by the association of two or three drugs with different mechanism of action. The most common application of this scheme includes a calcineurin inhibitor in combination with an antimetabolite and a minimum dose of steroids. Immunosuppressive therapy is also associated to an increased risk of infections and cancer development. For instance, each class of drugs is related to a different profile of toxicity. The choice of treatment protocol should take into account the clinical characteristics of the donor and recipient. Furthermore, this treatment may change anytime when clinical conditions result into complications.

Oxaliplatin Immune-Induced Syndrome Occurs With Cumulative Administration and Rechallenge: Single Institution Series and Systematic Review Study.

Oxaliplatin immune-induced syndrome (OIIS) is an uncommon, potentially life-threatening, side effect associated with oxaliplatin-based chemotherapy. The present study reports 5 original cases of OIIS and systematically reviewed the available published cases. We retrospectively analyzed the clinical archives of the Niguarda Cancer Center from 2009 to 2015 and conducted a search for OIIS using the PubMed database, followed by deeper investigation of the references of the recorded studies. We pooled our series with other reported cases for systematic review in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement using only English language as the selection criterion. A total of 61 OIIS cases were analyzed, the largest series reported to date. Of the 61 patients, 56 (91.8%) had received oxaliplatin for metastatic colorectal cancer. In 32 of the 61 patients (52.5%), OIIS was associated with grade 4 thrombocytopenia and in 4 (6.6%) with grade 4 anemia. OIIS was fatal in 4 patients. In 49 patients, oxaliplatin-induced immune system activation was tested using the Coombs test or by detection of antiplatelet antibodies and was positive in 87.7% of the patients. The average number of oxaliplatin cycles until the onset of OIIS was 16.7, and the number was significantly lower when oxaliplatin was administered as a rechallenge after a period of vacancy of treatment with this agent (4.6 cycles as rechallenge vs. 13.6 as first-time exposure; P < .00001). OIIS is triggered by cumulative administration of oxaliplatin, characteristically with a threefold earlier onset when the drug is administered as a rechallenge. Prompt identification of OIIS can be expected to reduce the risk of iatrogenic morbidity and mortality.

Is renal living-donor transplantation indicated in adult patients with orthotopic ileal neobladder? Lessons learned from a clinical case.

Renal transplantation is the treatment of choice for patients with end-stage renal disease and it has already been described in the literature in patients with orthotopic neobladders, mostly in the paediatric population. We report the first case of a living-donor renal graft in an adult patient with a orthotopic neobladder that was performed after radical cystectomy for urinary tuberculosis and reflux nephropathy. This patient experienced urologic and metabolic complications since the early posttransplant period.

Subclinical impairment of coronary flow velocity reserve assessed by transthoracic echocardiography in young renal transplant recipients.

BACKGROUND: In renal transplant recipients (RTR) an increased risk to develop cardiovascular injury is present. Transthoracic Doppler echocardiographic assessment of coronary flow velocity reserve (CFVR), a sensitive and minimally invasive technique, was recently employed to detect both macrovascular and microvascular coronary artery disease (CAD) in different clinical settings. The prevalence of coronary involvement in young adult RTR is still unknown. The aim of the study was to investigate the presence of early cardiovascular damage in asymptomatic young adult RTR. METHODS: Transthoracic Doppler echocardiographic-derived CFVR and common carotid intima-media thickness (IMT) were assessed in 25 asymptomatic young adult RTR (mean age 25.7+/-7.0 years; range 17.3-43.9) without CAD and 25 healthy controls. RESULTS: CFVR was lower in young adult RTR compared to controls (2.8+/-0.6 vs. 3.5+/-0.8; P<0.001), meanwhile left ventricular wall motion and common carotid IMT were comparable in both groups. We found a negative correlation between CFVR and age (r=-0.50; P=0.018) and months on dialysis (r=-0.54; P<0.01). CONCLUSIONS: Young adult RTR showed a reduced CFVR reflecting an impaired coronary microcirculation, which is significantly related to the age and duration of dialysis; coronary microvascular damage is detectable in the absence of changes in common carotid IMT. Non-invasive evaluation of CFVR by transthoracic stress echocardiography could be a reliable method for identification of early coronary microvascular involvement in young adult RTR.