An updated approach to the evaluation of the urinary sediment.

Examination of the urinary sediment (U-sed) is an important non-invasive, rapid, and inexpensive tool for the diagnosis and surveillance over time of renal diseases. In this Educational Review, we describe first how to collect, prepare, and examine urine samples in order to obtain reliable results. Then, we describe the U-sed findings in isolated microscopic hematuria, glomerular diseases, acute interstitial nephritis, acute kidney injury, reactivation of the BK virus in kidney transplant recipients, and crystalluric genetic diseases.

Post-Kidney Transplant Cancer: A Real-World Retrospective Analysis From a Single Italian Center.

We describe the epidemiology of cancer after kidney transplantation (KTx), investigating its risk factors and impact on therapeutic management and survival in KTx recipients (KTRs). The association between modification of immunosuppressive (IS) therapy after cancer and survival outcomes was analyzed. We collected data from 930 KTRs followed for 7 [1-19] years. The majority of KTRs received KTx from a deceased donor (84%). In total, 74% of patients received induction therapy with basiliximab and 26% with ATG. Maintenance therapy included steroids, calcineurin inhibitors, and mycophenolate. Patients with at least one cancer (CA+) amounted to 19%. NMSC was the most common tumor (55%). CA+ were older and had a higher BMI. Vasculitis and ADPKD were more prevalent in CA+. ATG was independently associated with CA+ and was related to earlier cancer development in survival and competing risk analyses (p = 0.01 and <0.0001; basiliximab 89 ± 4 vs. ATG 40 ± 4 months). After cancer diagnosis, a significant prognostic impact was derived from the shift to mTOR inhibitors compared to a definitive IS drug suspension (p = 0.004). Our data confirm the relevance of cancer as a complication in KTRs with ATG as an independent risk factor. An individualized choice of IS to be proposed at the time of KTx is crucial in the prevention of neoplastic risk. Finally, switching to mTORi could represent an important strategy to improve patient survival.

Post-Transplant Diabetes Mellitus in Kidney-Transplanted Patients: Related Factors and Impact on Long-Term Outcome.

This study aimed to investigate the prevalence and determinants of glucose metabolism abnormalities and their impact on long-term clinical outcomes in kidney transplant recipients (KTxps). A retrospective analysis of 832 KTxps (2004-2020) was performed. Patients were assessed at 1 (T1), 6 (T6), and 12 (T12) months post-transplantation and clinically followed for an average of 103 ± 60 months. At T6, 484 patients underwent an oral glucose tolerance test for the diagnosis of alterations in glucose metabolism (AMG+) or post-transplant diabetes mellitus (PTDM+). The prevalence of pre-transplant diabetes was 6.2%, with 22.4% of PTDM+ within the 1st year. Patients with AMG were older and exhibited altered lipid profiles, higher body mass index, and increased inflammatory indices. Age at transplantation, lipid profile, and inflammatory status were significant determinants of PTDM. Graft loss was unaffected by glucose metabolism alterations. Survival analysis demonstrated significantly worse long-term survival for KTxps with diabetes (pre- and PTDM+, p = 0.04). In a comparison of the ND and PTDM+ groups, no significant differences in death with a functioning graft were found. The AMG+ group exhibited worse survival (p < 0.001) than AMG-, even after excluding patients with diabetes mellitus. Future randomized controlled trials are necessary to delve deeper into this subject, specifically examining the effects of new antidiabetic treatments.

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.

Hepatitis C Virus Infection Increases the Risk of Developing Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

BACKGROUND AND RATIONALE: Chronic kidney disease and hepatitis C virus are prevalent in the general population worldwide, and controversy exists about the impact of HCV infection on the development and progression of kidney disease. DESIGN: A systematic review of the published medical literature was made to assess whether positive anti-HCV serologic status plays an independent impact on the development of chronic kidney disease in the adult general population. We used a random-effects model to generate a summary estimate of the relative risk of chronic kidney disease (defined by reduced glomerular filtration rate or detectable proteinuria) with HCV across the published studies. Meta-regression and stratified analysis were also conducted. RESULTS: Twenty-three studies (n = 2,842,421 patients) were eligible, and separate meta-analyses were performed according to the outcome. Pooling results of longitudinal studies (n = 9; 1,947,034 unique patients) demonstrated a relationship between positive HCV serologic status and increased incidence of chronic kidney disease, the summary estimate for adjusted hazard ratio was 1.43 (95% confidence interval 1.23; 1.63, P = 0.0001), and between-studies heterogeneity was noted (P value by Q test <0.0001). The risk of the incidence of chronic kidney disease associated with HCV, in the subset of Asian surveys, was 1.31 (95% confidence interval 1.16; 1.45) without heterogeneity (P value by Q test = 0.6). HCV positive serology was an independent risk factor for proteinuria; adjusted odds ratio, 1.508 (95% confidence intervals 1.19; 1.89, P = 0.0001) (n = 6 studies; 107,356 unique patients). CONCLUSIONS: HCV infection is associated with an increased risk of developing chronic kidney disease in the adult general population.

[Sulfamethoxazole crystalluria]. / Cristalluria a 'Fascine di grano': complicanza della terapia con sulfametossazolo?

Drug-induced crystalluria is a cause of acute renal failure that has not to be overlooked. Especially sulfonamides are known to be little solubles in acidic urine. Among these drugs, sulfadiazine produces the so-called shocks of wheat crystals, whose formation can be avoided by opportune hydration and alkalinization of the patient. Sulfamethoxazole is another drug of this class that has seldom been reported to cause a pleomorphic crystalluria. We report the case of two patients treated with sulfamethoxazole who developed a crystalluria that is very similar to the sulfadiazine one. Sulfamethoxazole is widely used in clinical practice in association with trimethoprim and it is known to cause acute renal failure, although little is known about the pathogenesis of this nephrotoxicity. Our cases, along with the cases previously reported, may suggest that sulphamethoxazole can act as a nephrotoxic agent through crystals production. Notably, in our cases, discontinuation of the drug led to disappearance of the crystals.

Chyluria associated with nephrotic-range proteinuria: pathophysiology, clinical picture and therapeutic options.

Chyluria denotes the urinary excretion of chyle, which is a lymphatic fluid rich in chylomicrons. Chyle flows from the intestinal lacteals to the left subclavian vein through the thoracic duct. When an abnormal connection between these structures and the urinary tract develops, chyluria appears. The syndrome is often associated with a nephrotic-range proteinuria, and this could be a wrong indication to perform renal biopsy. Chyluria is classified as parasitic or nonparasitic, the former being induced by lymphatic filariasis, whereas the latter is caused by medical, traumatic or inherited diseases. The patient usually reports excretion of milky urines, monolateral flank pain, malnutrition, weight loss and weakness. Urinalysis demonstrates lymphocyturia associated with chylomicrons and triglycerides in the supernatant. The diagnostic approach is aimed to define the site of lymphourinary fistula. A selective ureteral catheterization allows to collect urine samples from each kidney, demonstrating a monolateral source of proteins and lipids and making renal biopsy superfluous. Other diagnostic tools include nuclear magnetic resonance urography and lymphoangiography. Many therapeutic options have been proposed. Sclerosing solution instillation into the renal pelvis and laparoscopic renal pedicle disconnection are the invasive procedures most commonly employed. Among the medical alternatives, a low-fat diet supplemented with medium-chain triglycerides is often followed by complete clinical and biochemical remission.

Looking at appearance of urine before performing a renal biopsy in nephrotic syndrome.

Chyluria results from an abnormal connection between lymphatic bed and urinary tract, causing lymph leakage into the urine. The clinical picture often begins with the appearance of cloudy, milky urines accompanied by monolateral flank pain, malnutrition, weight loss and weakness. We report a case of chyluria that occurred in a young woman who was referred to our unit for nephrotic-range proteinuria. Before performing a renal biopsy, we found that urine analysis demonstrated a massive lipiduria. Therefore, we collected urine samples from each kidney with a selective ureteral catheterization, demonstrating a monolateral source of lipids and proteins. We suspended the renal biopsy and performed a lymphography that showed an inherited lymphangioma on the left lumbar lymphatic bed. Sclerosing solution instillation, renal pedicle lymphatic disconnection or laser therapy are invasive therapeutical options that may cause severe adverse effects. Instead of these procedures, a conservative therapy based on a low-fat diet supplemented with medium-chain triglycerides was chosen. This dietetic schedule was followed by complete resolution of proteinuria and lipiduria. The patient progressively gained body weight and improved quality of life. No relapses were observed after 3 years of follow-up. This case emphasizes the possible role of a noninvasive therapeutical option for patients with chyluria.

Crystalluria: prevalence, different types of crystals and the role of infrared spectroscopy.

BACKGROUND: Studies on the frequency of the different types of urinary crystals and the role of Fourier transform infrared microspectroscopy (FTIRM) for identification are few. We describe the results of a retrospective study on the prevalence and typology of crystalluria and on the role of FTIRM. METHODS: Urinary crystals were identified using the combined knowledge of crystal morphology, birefringence features and urine pH (combined approach). When this was inconclusive, FTIRM was performed. RESULTS: Crystalluria was found in 807 out of 9834 samples (8.2%). In 793, the combined approach identified "typical" crystals, while in 14 FTIRM was needed to identify "atypical" crystals. Among "typical crystals", calcium oxalate (75.9%), uric acid (25.9%) and amorphous urates (7.9%), alone or in combination, were the most frequent. Brushite, ammonium biurate and cystine were the most rare (0.1%-0.7%). FTIRM identified 12 of 14 atypical crystals: three crystals were due to a drug (amoxicillin, indinavir, doubtful phenytoloxamine); four were due to calcium oxalate mono- or bihydrate, uric acid bihydrate or struvite; five were due to calcium carbonate, Tamm-Horsfall glycoprotein, or rare salt combinations. CONCLUSIONS: Crystalluria is not rare and most crystals can be identified by the combined approach. Occasionally, identification of crystals will require FTIRM.

An Italian external quality assessment (EQA) program on urinary sediment.

BACKGROUND: EQA programs on urinary sediment are rare. We describe an EQA Italian program which started in 2001 and involves today more than 300 laboratories. METHODS: The program, which started with a questionnaire about the methodological aspects on urinary sediment, includes today four surveys per year. These ask the participants the identification and clinical associations of urinary sediment particles shown by colour images (surveys 1 and 3) and the diagnosis of clinical cases presented by both images and a short clinical history (surveys 2 and 4). The results of each survey are then scored and commented. RESULTS: Questionnaire (participants = 287): most methodological aspects were not dealt with properly. IDENTIFICATION: cells, lipids, casts and some contaminants were poorly known. However, when 27 particles were presented for the second time and 16 particles for the third time, the correct identification rate for most of them increased significantly. Clinical associations (No presented = 16): a correct answer was indicated by > or = 84% of participants for all particles but one. Clinical cases (No presented=4): lowest correct identification for urine contamination from genital secretion (77.3%), highest for ureteric stone (94.4%). CONCLUSIONS: Our program shows that EQA programs are both useful and needed.