[Examination of Urinary Sediment in a Patient with Lupus-Like HIV-Associated Immune Complex Kidney Disease (HIVICK) - Case Report and Review of the Literature].

Renal involvement is very common in patients with HIV infection. The phenotype varies from the most frequently "collapsing" variant of focal and segmental glomerulosclerosis (FSGS) to "lupus-like HIV-immune complex kidney disease" (HIVICK). The latter is characterized by a histological picture that recalls lupus nephropathy. Through a clinical case, we underline the importance of urinary sediment analysis in patients with suspected glomerulopathy. Findings such as the characteristic cells that show the typical appearance of Herpes virus (HSV) infection or LE cells have significantly supported the diagnosis of HIVICK. In light of the present observations, we suggest systematically carrying out a cytological examination of the urinary sediment to confirm diagnostic hypotheses of rare pathologies.

[Collapsing Glomerulopathy Secondary to Anabolic Steroids for Bodybuilding: A Case Series].

The abuse of anabolic androgenic steroids (AAS) for competitive (and non-competitive) purposes for bodybuilding practice is increasingly common. The consequences of these substances on the various organs are only partially known. Cases of FSGS following the use of AAS have been reported in the literature, even with evolution to ESKD. We describe three cases of bodybuilding athletes who presented alterations in renal function indices after taking AAS for a long time. Three renal biopsies were performed with histological diagnosis of FSGS collapsing variant. We examine the lesions observed on histological examination. Two athletes had rapid progression of renal disease requiring replacement therapy. The third one continues conservative treatment for chronic renal failure. We discuss the risks related to the intake of doping substances and how bodybuilders are exposed to different causes of kidney damage: anabolic steroids, supplements, and a high-protein diet.

Profile, Healthcare Resource Consumption and Related Costs in ANCA-Associated Vasculitis Patients: A Real-World Analysis in Italy.

INTRODUCTION: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare autoimmune diseases triggering inflammation of small vessels. This real-world analysis was focused on the most common AAV forms, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), to describe patients' demographic and clinical characteristics, therapeutic management, disease progression, and the related economic burden. METHODS: A retrospective analysis was conducted on administrative databases of a representative sample of Italian healthcare entities, covering approximately 12 million residents. Between January 2010 and December 2020, adult GPA patients were identified by payment waiver code or hospitalization discharge diagnosis, and MPA patients by payment waiver code with or without hospitalization discharge diagnosis. Clinical outcomes were evaluated through AAV-related hospitalizations, renal failure onset, and mortality. Economic analysis included healthcare resource utilization deriving from drugs, hospitalizations, and outpatient specialist services. The related mean direct costs year/patient were also calculated in patients stratified by presence/absence of glucocorticoid therapy and type of inclusion criterion (hospitalization/payment waiver code). RESULTS: Overall, 859 AAV patients were divided into GPA (n = 713; 83%) and MPA (n = 146; 17%) cohorts. Outcome indicators highlighted a clinically worse phenotype associated with GPA compared to MPA. Cost analysis during follow-up showed tendentially increased expenditures in glucocorticoid-treated patients versus untreated (overall AAV: €8728 vs. €7911; GPA: €9292 vs. €9143; MPA: €5967 vs. €2390), mainly driven by drugs (AAV: €2404 vs. €874; GPA: €2510 vs. €878; MPA: €1881 vs. €854) and hospitalizations. CONCLUSION: Among AAV forms, GPA resulted in a worse clinical picture, higher mortality, and increased costs. This is the first real-world pharmaco-economic analysis on AAV patients stratified by glucocorticoid use on disease management expenditures. In both GPA and MPA patients, glucocorticoid treatment resulted in higher healthcare costs, mostly attributable to medications, and then hospitalizations, confirming the clinical complexity and economic burden for management of patients with autoimmune diseases under chronic immunosuppression.

The Effect of Fracture Patterns, Pinning Configuration, Surgeon Experience and Subspecialty on Short-Term Radiological Outcomes of Pediatric Supracondylar Humeral Fractures Treated in the Prone Position: A Case-Series.

BACKGROUND: The most common treatment modality for supracondylar humerus fractures (SCHFs) in children is closed reduction and percutaneous pinning (CRPP). Nonetheless, debate persists regarding the optimal technique used. Therefore, the purpose of our study was to investigate the impact of surgeon experience, surgeon subspecialty and pin configuration on short-term radiological outcomes following CRPP of displaced SCHFs. METHODS: Patients less than 14 years of age who underwent CRPP for displaced SCHFs in the prone position between January 2018 and December 2022 were analyzed. Patients were separated into subgroups based on fracture type (low vs. high sagittal), pin configuration (lateral, cross, other), number and configuration of K-wires and first operator surgical experience. The following outcome measurements were collected: postoperative Baumann angle (BA), Shaft-Condylar angle (SCA), surgical duration (SD), duration of radiation exposure (DRE) and number of clinical and radiological follow-ups (FU). RESULTS: A total of 44 patients with a mean age of 6 ± 2.5 years were included in the final analysis. The mean post-operative BA and SCA were 74.8° ± 4.9° and 37.7° ± 10.2°, respectively. No significant differences were found in the post-operative Baumann's angle or SCA among the subgroups. Regarding secondary outcomes, no differences were found among each subgroup regarding SD, DRE and FUs. CONCLUSION: Short-term radiological outcomes following the treatment of SCHFs treated in the prone position are not affected by fracture patterns and pinning configuration, regardless of the surgeon's years of experience or subspecialty.

[Anti-MBG crescentic glomerulonephritis with negative immunofluorescence: case report and literature review].

Anti-glomerular basement membrane (anti-GBM) antibody disease is a rapidly progressive glomerulonephritis characterized by (i) positivity to anti-GBM in serum reacting with a specific antigen present in type IV collagen at both the glomerular and alveolar levels (ii) presence of crescent on light microscopy and positivity to linear deposits of IgG and C3 on immunofluorescence. In the classic variant, the clinic is that of a nephro-pneumological syndrome but there are variants. Rarely, the glomerular damage is pauci-immune. We describe a case of a variant in which there is anti-MBG positivity in serum but negative immunofluorescence and offer a review of the literature and potential treatments.

Next-Generation Sequencing (NGS) Analysis Illustrates the Phenotypic Variability of Collagen Type IV Nephropathies.

Mutations in COL4A3-A5 cause a spectrum of glomerular disorders, including thin basement membrane nephropathy (TBMN) and Alport syndrome (AS). The wide application of next-generation sequencing (NGS) in the last few years has revealed that mutations in these genes are not limited to these clinical entities. In this study, 176 individuals with a clinical diagnosis of inherited kidney disorders underwent an NGS-based analysis to address the underlying cause; those who changed or perfected the clinical diagnosis after molecular analysis were selected. In 5 out of 83 individuals reaching a molecular diagnosis, the genetic result was unexpected: three individuals showed mutations in collagen type IV genes. These patients showed the following clinical pictures: (1) familial focal segmental glomerulosclerosis; (2) end-stage renal disease (ESRD) diagnosed incidentally in a 49-year-old man, with diffuse cortical calcifications on renal imaging; and (3) dysmorphic and asymmetric kidneys with multiple cysts and signs of tubule-interstitial defects. Genetic analysis revealed rare heterozygote/compound heterozygote COL4A4-A5 variants. Our study highlights the key role of NGS in the diagnosis of inherited renal disorders and shows the phenotype variability in patients carrying mutations in collagen type IV genes.

The risks associated with percutaneous native kidney biopsies: a prospective study.

BACKGROUND: The known risks and benefits of native kidney biopsies are mainly based on the findings of retrospective studies. The aim of this multicentre prospective study was to evaluate the safety of percutaneous renal biopsies and quantify biopsy-related complication rates in Italy. METHODS: The study examined the results of native kidney biopsies performed in 54 Italian nephrology centres between 2012 and 2020. The primary outcome was the rate of major complications 1 day after the procedure, or for longer if it was necessary to evaluate the evolution of a complication. Centre and patient risk predictors were analysed using multivariate logistic regression. RESULTS: Analysis of 5304 biopsies of patients with a median age of 53.2 years revealed 400 major complication events in 273 patients (5.1%): the most frequent was a ≥2 g/dL decrease in haemoglobin levels (2.2%), followed by macrohaematuria (1.2%), blood transfusion (1.1%), gross haematoma (0.9%), artero-venous fistula (0.7%), invasive intervention (0.5%), pain (0.5%), symptomatic hypotension (0.3%), a rapid increase in serum creatinine levels (0.1%) and death (0.02%). The risk factors for major complications were higher plasma creatinine levels [odds ratio (OR) 1.12 for each mg/dL increase, 95% confidence interval (95% CI) 1.08-1.17], liver disease (OR 2.27, 95% CI 1.21-4.25) and a higher number of needle passes (OR for each pass 1.22, 95% CI 1.07-1.39), whereas higher proteinuria levels (OR for each g/day increase 0.95, 95% CI 0.92-0.99) were protective. CONCLUSIONS: This is the first multicentre prospective study showing that percutaneous native kidney biopsies are associated with a 5% risk of a major post-biopsy complication. Predictors of increased risk include higher plasma creatinine levels, liver disease and a higher number of needle passes.

[Inflammation in kidney diseases].

The term "inflammation" is certainly one of the oldest medical terms still in use. However, its meaning has changed over the centuries. This work gives a historical and critical review of the concept of inflammation, with special reference to kidney diseases. Over time the definition of inflammation has shifted from a pure collection of symptoms to a histopathological definition, characterized by the tissue "inflammatory infiltrates" and different subcategories according to the cell type involved. The advantages of this classification are the generally good response to corticosteroids (with only a few exceptions) and the availability of specific drugs for each inflammatory infiltrate. Finally, a "molecular" definition of inflammation has arisen, where the inflammatory infiltrates make room to a plethora of plasma mediators. The authors show that the use of plasma biomarkers as a tool to define inflammatory state leads to net inflation of the number of "inflammatory" diseases - an effect that shows clearly in the field of nephrology.

The number of nephrons in different glomerular diseases.

BACKGROUND: The total number of nephrons has been measured mainly from post-mortem studies and only in selected populations. Data from living subjects are scanty, and direct comparisons among different glomerular diseases are lacking. The present work exploits modern methodology to estimate the total nephron number in glomerulopathies with prevalent proteinuria/nephrotic syndrome versus glomerulopathies with nephritic syndrome (IgA nephropathy (IgAN), lupus nephritis), thus extending previous observations about the number and function of glomeruli in different physiological and pathological states. METHODS: This is a retrospective study based on one hundred and seven patients who have undergone renal biopsy. The glomerular density has been estimated from the biopsy specimens and the total cortical volume has been obtained from ultrasound recordings. Stereological methods have been applied to calculate the total number of nephrons and their volume. The correlation between clinical parameters and quantitative morphological data have studied using the Pearson correlation coefficient (r). RESULTS: The total number of nephrons inversely correlated with the systolic blood pressure (r = -0.4, p < 0.05). In proteinuric diseases, such as focal segmental glomerulo-sclerosis (FSGS), membranous nephropathy (MN) and diabetes, the change in estimated GFR (eGFR) directly correlated with the total number of non-sclerotic glomeruli (NSG) (r = 0.62, p < 0.01), whereas in nephritic syndrome no significant correlation was observed. The alterations in eGFR occurring in nephritic syndromes such as IgAN cannot be explained on the basis of the number of NSG. DISCUSSION: The fusion of the podocyte foot-processes that typically occurs in purely proteinuric diseases does not modify the glomerular filtration rate: therefore in these situations, the change in eGFR depends mainly on the number of available glomeruli. On the other side, the eGFR decrease occurring in nephritic syndromes, such as IgAN, cannot be explained simply on the basis of the number of NSG and likely depends on the substantial involvement of the mesangial axis. Future studies should verify whether these changes are reversible with appropriate therapy, thus reversing eGFR decrease.

Cellular and subcellular localization of uncoupling protein 2 in the human kidney.

The uncoupling protein-2 (UCP2) is an anion transporter that plays a key role in the control of intracellular oxidative stress. In animal models UCP2 downregulation has several pathological sequelae, particularly affecting the vasculature and the kidney. Specifically, in these models kidney damage is highly favored in the absence of UCP2 in the context of experimental hypertension. Confirmations of these data in humans awaits further information, as no data are yet available concerning the cell-type and subcellular expression in the human kidney. In the present study, we aimed to characterize the UCP2 protein distribution in human kidney biopsies. In humans UCP2 is mainly localized in proximal convoluted tubule cells, with an intracytoplasmic punctate staining. UCP2 positive puncta are often localized at the interface between the endoplasmic reticulum and the mitochondria. Glomerular structures do not express UCP2 at detectable levels. The expression of UCP2 in proximal tubular cells may explain their relative propensity to damage in pathological conditions including the hypertensive disease.

Urate-Lowering Agents in Asymptomatic Hyperuricemia: Role of Urine Sediment Analysis and Musculoskeletal Ultrasound.

Current urate-lowering therapy (ULT) includes three direct acting drugs (allopurinol, febuxostat, Rasburicase) and at least four 'indirect' drugs with other important targets (canagliflozin, losartan, fenofibrate and sevelamer). Moreover, the alcalinization of urines using bicarbonate can be used to dissolve urate crystals and the clinician may discontinue several drugs are known to increase serum levels of uric acid, such as diuretics, aspirin, cyclosporine, theophylline, mycophenolate and ACE inhibitors. While there is a consensus to start ULT in cases of symptomatic hyperuricemia (gout, urate-nephrolithiasis), the very frequent conditions of asymptomatic hyperuricemia remains a major conundrum. The effect of asymptomatic hyperuricemia on kidney function has had fluctuating positions over decades. The conflicting results might indicate: (i) the presence of counterbalancing positive and negative effects on kidney function of both serum uric acid and urate-lowering agents, (ii) the presence of a subpopulation of patients, as yet unidentified, which could truly benefit from a urate-lowering therapy. Therefore, today the treatment of asymptomatic hyperuricemia is not recommended nor excluded by current guidelines. Here we suggest that a possible guide for the treatment of asymptomatic hyperuricemia might be the presence of urate crystals in the urine sediment and/or signs of asymptomatic articular damage by urates, identified by musculo-skeletal ultrasound. Moreover, a watchful analysis of the trend in creatinine/eGFR, proteinuria or urate levels might also guide the clinician. Initiation of ULT and follow-up in cases of asymptomatic hyperuricemia should consider urine sediment analysis, musculoskeletal ultrasound and trends in creatinine, proteinuria and serum urate levels.

A cross-sectional study on the relationship between hematological data and quantitative morphological indices from kidney biopsies in different glomerular diseases.

BACKGROUND: The classical approach to the analysis of kidney biopsies is based on semi-quantitative scores of the amount of sclerosis, inflammatory infiltrate, fibrosis and vascular damage. However, advanced renal lesions may be accompanied by a paucity of clinical features and, conversely, important clinical abnormalities may be accompanied by minimal histopathological changes. The objective of this study is to correlate new, semiautomatic, quantitative features of kidney biopsies (e.g. fractal analysis) with clinical and hematological parameters using a cross-sectional design. METHODS: Whole slide images from sixty-seven biopsies of patients diagnosed for diabetic nephropathy, hypertensive nephropathy, focal segmental glomerulosclerosis (FSGS) or IgA nephropathy have been used. The images have been semi-automatically quantified in the ImageJ environment, in order to derive the glomerular density, the tubular density, the number of tubules per glomerulus and the fractal dimension of the tubular lumen in the cortex (an index of complexity of the tubular lumen). For each patient, hemato-chemical data have been retrieved, including the uric acid level and the creatinine-based eGFR. RESULTS: A linear relationship between eGFR and glomerular density was observed in hypertension and FSGS, but not in diabetic nephropathy. Conversely, the eGFR correlated with the tubular density across different glomerular conditions. Moreover, the tubular density was linearly correlated with uric acid levels in different pathological conditions. The fractal dimension of tubular lumen was correlated with the eGFR but only in hypertensive patients. Finally, blood pressure was not correlated to any of the morphological indices tested. CONCLUSIONS: We propose the use of the fractal dimension as a new morphological descriptor of the nephron integrity.

[Role of directional power-Doppler in the identification of renovascular malformations]. / Ruolo del power-Doppler direzionale nell'identificazione di malformazioni vascolari renali.

OBJECTIVE: The directional power-Doppler (dPD) is a useful tool in evaluating the renal vascularization for its high sensibility and availability. Renal vascular malformations like the arteriovenous fistulas (avF) are rare and their real incidence is unknown. We evaluated the diagnostic role of dpD in renal avF. MATERIAL AND METHODS: From January 1999 to 2002 1518 subjects (875 males, 643 females, mean age: 62 years, range: 22-87 years) have been studied by both B-mode ultrasound and by dpD. All ultrasonographies were taken with a Toshiba Power Vision 6000 by the same skilled operator. RESULTS: Among 1518 patients examined, 17 avF have been identified (diameter range: 3-18 mm) by using dPD. Four of these have an unclear etiology (congenital?) and they have been considered idiopathic. On the contrary, five are acquired: two are caused by renal biopsy, two by renal tumors and one by ureteral stent positioning, respectively. Eight patients, all affected by polycystic kidney disease, showed multiple avF. The four subjects with idiopathic avF are suffering from chronic renal failure (CRF--CrCl = 8-35 ml/min); on the contrary, among patients with polycystic kidney, five of them are on CRF (CrCl = 14-27 ml/min), three have normal renal function. The acquired avF caused by renal biopsy or by ureteral catheterization have spontaneously disappeared after 15-20 days from the causative event. CONCLUSIONS: The dPD allows to individualize the arteriovenous malformations of renal vasculature which could be underestimated or not evidenced by other instrumental methods.