Disruption of the glomerular basement membrane associated with nutcracker syndrome and double inferior vena cava in Noonan syndrome: a case report.

BACKGROUND: Nutcracker syndrome (NCS) is characterized by compression of the left renal vein (LRV) between the aorta and the superior mesenteric artery. While rare, NCS was reported to be accompanied by double inferior vena cava (IVC). We herein report a case of Noonan syndrome (NS) with double IVC who presented with macrohematuria and proteinuria. CASE PRESENTATION: The patient was a 23-year-old man, who had been diagnosed with NS due to RIT1 mutation, after showing foamy macrohematuria 3 weeks previously. A physical examination revealed low-set ears and a webbed neck. A urinalysis showed hematuria and proteinuria, and urinary sediments showed more than 100 isomorphic red blood cells per high-power field. His proteinuria and albuminuria concentrations were 7.1 and 4.5 g/g⋅Cr, respectively. Three-dimensional contrast-enhanced computed tomography (CT) showed double IVC and narrowing of the LRV after interflow of the left IVC. The aortomesenteric angle on a sagittal reconstruction of the CT image was 14.7°. Cystoscopy revealed a flow of macrohematuria from the left ureteral opening. On Doppler ultrasonography, there was scant evidence to raise the suspicion of the nutcracker phenomenon. Since severe albuminuria continued, a left kidney biopsy was performed. Light microscopy showed red blood cells in Bowman's space and the tubular lumen. Electron microscopy revealed disruption of the glomerular basement membrane (GBM). Vulnerability of the GBM was suspected and a genetic analysis revealed a heterozygous mutation at c.4793 T > G (p.L1598R) in the COL4A3 gene. Screening for coagulation disorders revealed the factor VIII and von Willebrand factor (vWF) values were low, at 47.6 and 23%, respectively. A multimer analysis of vWF showed a normal multimer pattern and he was diagnosed with von Willebrand disease type 1. As the bleeding tendency was mild, replacement of factor VIII was not performed. His macrohematuria and proteinuria improved gradually without treatment, and his urinalysis results have been normal for more than 6 months. CONCLUSIONS: The present case showed macrohematuria and proteinuria due to NCS in NS with double IVC and von Willebrand disease type 1. The macrohematuria and proteinuria originated from glomerular hemorrhage because of vulnerability of the GBM due to COL4A3 mutation.

Pathophysiology of COVID-19-associated acute kidney injury.

Although respiratory failure and hypoxaemia are the main manifestations of COVID-19, kidney involvement is also common. Available evidence supports a number of potential pathophysiological pathways through which acute kidney injury (AKI) can develop in the context of SARS-CoV-2 infection. Histopathological findings have highlighted both similarities and differences between AKI in patients with COVID-19 and in those with AKI in non-COVID-related sepsis. Acute tubular injury is common, although it is often mild, despite markedly reduced kidney function. Systemic haemodynamic instability very likely contributes to tubular injury. Despite descriptions of COVID-19 as a cytokine storm syndrome, levels of circulating cytokines are often lower in patients with COVID-19 than in patients with acute respiratory distress syndrome with causes other than COVID-19. Tissue inflammation and local immune cell infiltration have been repeatedly observed and might have a critical role in kidney injury, as might endothelial injury and microvascular thrombi. Findings of high viral load in patients who have died with AKI suggest a contribution of viral invasion in the kidneys, although the issue of renal tropism remains controversial. An impaired type I interferon response has also been reported in patients with severe COVID-19. In light of these observations, the potential pathophysiological mechanisms of COVID-19-associated AKI may provide insights into therapeutic strategies.

Treatment and Management of Loin Pain Hematuria Syndrome.

PURPOSE OF REVIEW: Loin pain hematuria syndrome (LPHS) is rare and seldom diagnosed, yet it has a particularly significant impact on those affected. This is a review of the latest and seminal evidence of the pathophysiology and diagnosis of LPHS and presents the typical clinical presentation and treatment options available. RECENT FINDINGS: LPHS is typically found in young women with characteristic symptoms, including severe recurrent flank pain and gross or microscopic hematuria. The majority of patients will experience crippling pain for many years without effective therapy, often requiring frequent use of narcotic medication. However, the lack of conclusive pathophysiology, in conjunction with the rarity of LPHS, has prohibited the development and trial of definitive treatment options. Nevertheless, in order to combat this rare but severe disease, management strategies have continued to evolve, ranging from conservative measures to invasive procedures. This review presents an overview of the current hypotheses on the pathophysiology of LPHS in addition to summarizing the management strategies that have been utilized. Only 30% of LPHS patients will experience spontaneous resolution, whereas the majority will continue to face chronic, crippling pain. Several methods of treatment, including invasive and non-invasive, may provide an improved outcome to these patients. Treatment should be individually tailored and multi-disciplinary in nature. Further research is required to further elucidate the pathophysiology and develop new, specific, treatment options.

Prostatic Artery Embolization in Refractory Hematuria of Prostatic Origin.

Hematuria of prostatic origin has multiple etiologies including benign prostatic hyperplasia (BPH), iatrogenic urological trauma, prostate cancer, and radiation therapy. Hematuria secondary to benign prostatic hyperplasia can occur because of the increased vascularity of the primary gland, itself, or because of the vascular re-growth following a transurethral resection of the prostate. Prostatic hematuria usually resolves with conservative measures; however, refractory hematuria of prostatic origin may require hospitalization with treatment with blood transfusions, repeated indwelling urinary catheterization, and continuous bladder irrigation. Prostate artery embolization is an emerging minimally invasive procedural therapy for men with BPH that was originally utilized for the treatment of refractory hematuria of prostatic origin . This article aims to summarize the currently available evidence around prostate artery embolization for the treatment of refractory hematuria of prostatic origin.

Clinical and pathological findings of SARS-CoV-2 infection and concurrent IgA nephropathy: a case report.

BACKGROUND: Since the Coronavirus Disease 2019 (COVID-19) outbreak, there is accumulating data on the clinical characteristics, treatment strategies and prognosis of COVID-19 in patients with concurrent renal disease. Postmortem investigations reveal renal involvement in COVID-19, and most recently, several biopsy researches reveal that acute tubular injury, as well as glomerular nephropathy such as collapsing glomerulopathy were common histological findings. However, to our best knowledge, there is limited data regarding IgA nephropathy in the setting of COVID-19. CASE PRESENTATION: In the present case, we report a 65-year old Chinese woman who presented with dark-colored urine, worsening proteinuria and decreased renal function after COVID-19 infection. She received a renal biopsy during COVID-19 infection. The renal biopsy revealed IgA nephropathy without any evidence for SARS-Cov-2. The findings suggest that the renal abnormalities were a consequence of exacerbation of this patient's underlying glomerular disease after COVID-19 infection. After a regimen of 3-day course of glucocorticoid and angiotensin II receptor blocker therapy, the patient recovered and remained stable upon follow-up. CONCLUSIONS: It is important to consider the underlying glomerular disease exacerbation as well as virus induced injury when dealing with renal abnormalities in patients with COVID-19. A kidney biopsy may be indicated to exclude a rapidly progressive glomerular disease.

C3-glomerulonephritis in New Zealand - a case series.

BACKGROUND: C3-glomerulonephritis can lead to progressive renal impairment from complement-mediated glomerular injury. Incidence and outcomes of C3-glomerulonephritis are not known in the New Zealand population. METHODS: We reviewed all cases of C3-glomerulonephritis from the past 10 years at a tertiary referral centre in New Zealand. Descriptive information on baseline characteristics and clinical outcomes was collected. RESULTS: Twenty-six patients were included (16 men; mean ± SD age 44 ± 25 years) with a median follow-up of 30 months. Disease incidence was 1.3 cases per million individuals, of which 42% were Pacific Islanders. Most patients presented with renal impairment, with a median (IQR) creatinine at diagnosis of 210 (146-300) µmol/L, and 11 (42%) patients presented with nephrotic syndrome. Seven (27%) patients progressed to end stage renal disease and 2 (8%) had died. End stage renal disease occurred in 20% of patients treated with immunosuppression and in 50% of those not treated. Complete remission was seen in 25% of patients treated with some form of immunosuppression and in 17% of those not treated. CONCLUSIONS: Our results are consistent with previous descriptions of C3-glomerulonephritis. There was a suggestion of better clinical outcomes in patients treated with immunosuppression. There was a higher disease incidence in Pacific Islanders, which may indicate an underlying susceptibility to complement dysfunction in this population.

An overview of the multi-pronged approach in the diagnosis of Alport syndrome for 22 children in Northeast China.

BACKGROUND: Alport syndrome (AS) is a kind of progressive hereditary nephritis induced by mutations of different genes that encode collagen IV. The affected individuals usually develop hematuria during childhood, accompanying with gradual deterioration of renal functions. In this study, the multi-pronged approach was employed to improve the diagnosis of AS. METHODS: Twenty-two children were diagnosed and treated at the Department of Pediatric Nephrology of Jilin University First Hospital between January 2017 and January 2020 using the multi-pronged approach. The following information was collected from patients, including age of onset, age at diagnosis, clinical manifestations, family history, renal pathology and genotype. RESULTS: All these 22 children were diagnosed with Alport syndrome according to the diagnostic criteria formulated by the Japanese Society of Nephrology (2015), among them, only 13 children met the diagnostic criteria released in 1988. All the 22 patients presented with hematuria, and proteinuria to varying degrees was observed in some patients. Three children suffered from hearing loss, but no child in the cohort had any visual problem or renal failure. Meanwhile, five patients were estimated to be at Stage 2, whereas the remaining 17 cases were at Stage 0. Renal biopsies were performed in 18 patients, including 14 showing glomerular basement membranes (GBM)-specific abnormalities. Moreover, 13 children were detected with mutations of genes encoding collagen IV. CONCLUSIONS: The multi-pronged approach helps to improve the diagnosis of AS. Most patients do not have renal failure during childhood, but close assessment and monitoring are necessary. Also, the advancements in treatment are reviewed.

Macroscopic hematuria as a risk factor for hypertension in ageing people with hemophilia and a family history of hypertension.

Ageing people with hemophilia (PWH) have a higher prevalence of hypertension than the general population. This study aimed to determine whether macroscopic hematuria was associated with hypertension in PWH in a post hoc analysis using data from a cross-sectional study conducted by the ADVANCE Working Group (the H3 study), which included PWH ≥ 40 years of age. Data from 16 contributing centers, located in 13 European countries and Israel, were analyzed using logistic regression models. Of 532 recruited PWH in the H3 study, 117 had hypertension and a positive family history of hypertension (hypertension FH+), 75 had hypertension and a negative family history of hypertension (hypertension FH-), 290 had no diagnosis of hypertension, and the remaining 50 had missing hypertension data. Logistic regressions showed that macroscopic hematuria was associated with hypertension FH+, both in the univariate (OR = 1.84 [1.17-2.90], P = .01) and in the multivariate model (OR = 1.80 [1.03-3.16], P = .04). Macroscopic hematuria was not associated with hypertension FH-. Moreover, in a multivariate logistic regression the odds of hypertension FH+ were increased with the number of macroscopic hematuria episodes. The association between macroscopic hematuria and hypertension was significant for PWH with a family history of hypertension.

About the correct definition of acanthocytes for their use as markers of glomerular haematuria / Sobre la correcta definición de los acantocitos para su uso como marcadores de hematuria glomerular

Acanthocytes, when≥5% of urinary erythrocytes examined, are considered as the most reliable marker of glomerular haematuria. However, some uncertainties still exist in the literature about their morphological definition. The aim of this paper is to discuss this topic and to suggest a univocal definition of acanthocytes as erythrocytes with the shape of a ring with one or more protrusions

Los acantocitos, cuando son≥5% de los eritrocitos urinarios examinados, se consideran el marcador más fiable de la hematuria glomerular. Sin embargo, todavía existen algunas incertidumbres en la literatura acerca de su definición morfológica. El objetivo de este artículo es discutir este tema y proponer una definición unívoca de los acantocitos como eritrocitos con la forma de un anillo con una o más protuberancias

Renal autotransplantation results in pain resolution after left renal vein transposition.

Left renal vein transposition is often the preferred treatment of nutcracker syndrome. However, pain returns in some patients despite surgery. One solution to this problem is renal autotransplantation. Here we report our initial results of renal autotransplantation in patients with persistent flank pain despite a previous left renal vein transposition. We used the University of Wisconsin loin pain hematuria syndrome test as a diagnostic maneuver to determine who may benefit from renal autotransplantation; this procedure subsequently resulted in complete pain resolution in all three patients. All patients underwent successful renal autotransplantation and remain pain free. These cases support the test as a diagnostic maneuver to determine which patients may benefit from renal autotransplantation.

Comparison of Multipulse Laser Vaporesection versus Plasmakinetic Resection for Treatment of Benign Prostate Obstruction.

We aimed to compare the efficacy and safety of Multipulse laser vaporesection of the prostate (MPVP) versus plasmakinetic resection of the prostate (PKRP) for treatment of patients with benign prostate obstruction (BPO) in a prospective trial. From January 2016 to April 2017, a total of 144 patients were included in the cohort study, of whom 73 patients underwent MPVP and 71 underwent PKRP. All patients received pre-operative evaluation and followed up at 1, 3, 6 and 12 months postoperatively. Baseline characteristics, perioperative data and postoperative outcomes were compared. Early (within 30 days postoperatively) and late complications were also recorded. Preoperative data, including age, prostate volume, international prostate symptom score (IPSS), International Index of Erectile Function Questionnaires (IIEF-5), the rate of anticoagulants use, Charlson comorbidity index were similar in two groups. Peri-operative parameters, including the rate of transfusion, and decrease in hemoglobin level were comparable. The operative time, the duration of catheterization and length of hospital stay were significantly shorter in the MPVP group. The voiding parameters and the quality-of-life scores (QoL) improved significantly in both groups postoperatively. There was a significantly difference in QoL at 1-year in the MPVP group (p < 0.001), under mixed model analysis with random effect and Bonferroni correction. There were no significant differences in improvement of IPSS, Qmax, IIEF-5, residual prostate volume ratio and PSA level reduction at the 1-year follow-up. MPVP was significantly superior to PKRP in terms of a reduction in overall complication rate (21.9% vs 45.0%, p = 0.004). Both treatments led to comparable symptomatic improvements. MPVP demonstrates satisfactory efficiency, shorter catheterization time and shorter hospital stay. Our data revealed that MPVP may be a promising technique which is safe and favorable alternative for patients with BPO.

Pathologic glomerular characteristics and glomerular basement membrane alterations in biopsy-proven thin basement membrane nephropathy.

BACKGROUND: Thin basement membrane nephropathy (TBMN) is diagnosed by diffuse thinning of the glomerular basement membrane (GBM) without any clinical and pathologic findings of Alport syndrome and the other renal diseases. TBMN is characterized clinically by benign familial hematuria but rarely develops into end-stage renal disease. METHODS: In 27 cases of biopsy-proven TBMN, we evaluated the pathologic characteristics of TBMN, and examined the correlation between these pathologic characterizations and renal dysfunction. RESULTS: All patients had hematuria, and 21 patients (77.8%) had proteinuria. In six patients (28.6%) who were more than 50 years of age, the estimated glomerular filtration rate (eGFR) decreased from G3a to G4 in the chronic kidney disease stage. Pathologically, an irregular decrease in intensity of type IV collagen α5(IV) chain was seen in GBM, and irregular thinning with diffuse rough etched images was observed on the GBM surface with several sizes of holes by low-vacuum scanning electron microscopy. The glomerular morphology of TBMN was characterized by an increased number of small glomerular capillaries with an increased extracellular matrix (ECM). These characteristic morphologic alterations were evident from a young age in patients with TBMN, but were not correlated directly with the decrease of eGFR, the degree of hematuria, and proteinuria. The decrease of eGFR in patients with TBMN who were more than 50 years of age might be primarily mediated by arteriolosclerosis-associated glomerulosclerosis and interstitial fibrosis. CONCLUSION: Characteristic pathological glomerular findings and GBM alterations occurred from a young age but were not associated directly with renal impairment in biopsy-proven TBMN.

Glomerular isolated microscopic hematuria: urinary features and long term follow-up of a selected cohort of patients.

BACKGROUND: Isolated microscopic hematuria is a condition characterized by the presence in the urine of an "abnormal" number of erythrocytes in the absence of proteinuria. Several studies have been published on this condition, but with heterogeneous inclusion criteria and variable outcomes at follow-up. In this retrospective study, we describe a selected and homogenous cohort of patients who presented with isolated microscopic hematuria of glomerular origin. METHODS: We included in the study patients with isolated microscopic hematuria of glomerular origin (> 1 erythrocyte/high power field at 400× and ≥ 40% dysmorphic erythrocytes and/or ≥ 5% acanthocytes and proteinuria ≤ 150 mg/24 h) with a follow-up of > 60 months from the first documentation of microscopic hematuria. RESULTS: Forty-two patients (M 12, F 30, age at presentation 14-68 years, eGFR < 60 ml/min/1.73 m2: 1 patient) were included. During a medium term follow-up, microscopic hematuria was persistent in 25 patients (59.5%), transiently absent in 17 (40.5%), always glomerular in 16 patients (38.1%), and occasionally non-glomerular in 26 (61.9%); proteinuria, observed in 16 patients (38.1%), was always transient and < 500 mg/24 h. At the end of a follow-up of 181.8 ± 97.9 (median 168) months, only 2 patients (4.8%) had eGFR < 60 ml/min/1.73 m2, one of whom had reduced eGFR already at presentation. CONCLUSIONS: This study on a small but selected and homogeneous cohort of patients with isolated microscopic hematuria of glomerular origin demonstrates that urinary features can transiently change over time and that the renal outcome is good.

De Novo IgA Nephropathy in a Renal Allograft.

Posttransplant glomerulonephritis is a complication of kidney transplant that can impair graft function and long-term graft survival. De novo immunoglobulin A disease in kidney allografts appears to be much less common than the recurrent disease, and in most cases it is diagnosed in protocol biopsies with no clinical evidence of disease or in association with other renal transplant pathologies such as chronic rejection. We present a case of de novo immunoglobulin A nephropathy presenting with overt proteinuria, microscopic hematuria, and progressive deterioration of renal function 30 months after renal transplant.

Hematuria and Renal Outcomes in Patients With Diabetic Chronic KidneyDisease.

BACKGROUND: Hematuria may indicate nondiabetic renal disease in diabetic chronic kidney disease (CKD). However, some studies have reported that hematuria is noted in diabetic nephropathy and is associated with albuminuria. Hematuria is a risk factor for end-stage renal disease in glomerulonephritis, but its prognostic value in diabetic CKD is unknown. We investigated the factors associated with hematuria and the prognostic value of hematuria in patients with diabetic CKD. MATERIAL AND METHODS: We included 1958 patients with type 2 diabetes and CKD stages 1-5, and 111 patients underwent renal biopsy. Patients in the biopsied cohort were younger and had more severe proteinuria, compared with those in the total cohort; hematuria was associated with nondiabetic renal disease. RESULTS: In the total cohort, hematuria was observed in 15.0% of the patients and was associated with young age, a lower estimated glomerular filtration rate, proteinuria, high blood pressure and short diabetes duration. Hematuria was significantly associated with an increased risk (hazard ratio 1.39, 95% CI: 1.10-1.76, P < 0.001) of end-stage renal disease, particularly in patients with CKD stages 1-3 or a urine protein-to-creatinine ratio of <1,500mg/g (P for interaction < 0.05). The odds ratio of hematuria for rapid renal progression was 1.81 (95% CI: 1.29-2.53, P < 0.001). CONCLUSIONS: Hematuria is associated with nondiabetic renal disease in biopsied patients with diabetic CKD and is associated with an increased risk of end-stage renal disease in patients with early diabetic CKD.

Evaluation and Management of Gross Hematuria in Autosomal Dominant Polycystic Kidney Disease: A Point of Care Guide for Practicing Internists.

Gross hematuria is common in autosomal dominant polycystic kidney disease (ADPKD). It is an alarming symptom and may be the first manifestation of ADPKD. Cyst hemorrhage is a frequent cause of hematuria in ADPKD while other differential diagnoses include cyst infection, urinary tract infection, renal stones and an underlying malignancy. Knowledge of the precipitating factors and clinical presentation of these conditions will help practicing internists in performing an appropriate evaluation and management of these entities and their complications, as well as executing timely referrals to subspecialists when indicated.

Development of a prediction model for late urinary incontinence, hematuria, pain and voiding frequency among irradiated prostate cancer patients.

BACKGROUND AND PURPOSE: Incontinence, hematuria, voiding frequency and pain during voiding are possible side effects of radiotherapy among patients treated for prostate cancer. The objective of this study was to develop multivariable NTCP models for these side effects. MATERIAL AND METHODS: This prospective cohort study was composed of 243 patients with localized or locally advanced prostate cancer (stage T1-3). Genito-urinary (GU) toxicity was assessed using a standardized follow-up program. The GU toxicity endpoints were scored using the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE 3.0) scoring system. The full bladder and different anatomical subregions within the bladder were delineated. A least absolute shrinkage and selection operator (LASSO) logistic regression analysis was used to analyze dose volume effects on the four individual endpoints. RESULTS: In the univariable analysis, urinary incontinence was significantly associated with dose distributions in the trigone (V55-V75, mean). Hematuria was significantly associated with the bladder wall dose (V40-V75, mean), bladder dose (V70-V75), cardiovascular disease and anticoagulants use. Pain during urinating was associated with the dose to the trigone (V50-V75, mean) and with trans transurethral resection of the prostate (TURP). In the final multivariable model urinary incontinence was associated with the mean dose of the trigone. Hematuria was associated with bladder wall dose (V75) and cardiovascular disease, while pain during urinating was associated with trigone dose (V75) and TURP. No significant associations were found for increase in voiding frequency. CONCLUSIONS: Radiation-induced urinary side effects are associated with dose distributions to different organs as risk. Given the dose effect relationships found, decreasing the dose to the trigone and bladder wall may reduce the incidence of incontinence, pain during voiding and hematuria, respectively.