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Nature Reviews. Disease Primers Nov 2023IgA nephropathy (IgAN), the most prevalent primary glomerulonephritis worldwide, carries a considerable lifetime risk of kidney failure. Clinical manifestations of IgAN... (Review)
Review
IgA nephropathy (IgAN), the most prevalent primary glomerulonephritis worldwide, carries a considerable lifetime risk of kidney failure. Clinical manifestations of IgAN vary from asymptomatic with microscopic or intermittent macroscopic haematuria and stable kidney function to rapidly progressive glomerulonephritis. IgAN has been proposed to develop through a 'four-hit' process, commencing with overproduction and increased systemic presence of poorly O-glycosylated galactose-deficient IgA1 (Gd-IgA1), followed by recognition of Gd-IgA1 by antiglycan autoantibodies, aggregation of Gd-IgA1 and formation of polymeric IgA1 immune complexes and, lastly, deposition of these immune complexes in the glomerular mesangium, leading to kidney inflammation and scarring. IgAN can only be diagnosed by kidney biopsy. Extensive, optimized supportive care is the mainstay of therapy for patients with IgAN. For those at high risk of disease progression, the 2021 KDIGO Clinical Practice Guideline suggests considering a 6-month course of systemic corticosteroid therapy; however, the efficacy of systemic steroid treatment is under debate and serious adverse effects are common. Advances in understanding the pathophysiology of IgAN have led to clinical trials of novel targeted therapies with acceptable safety profiles, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, as well as blockade of complement components.
Topics: Humans; Glomerulonephritis, IGA; Antigen-Antibody Complex; Galactose; Immunoglobulin A
PubMed: 38036542
DOI: 10.1038/s41572-023-00476-9 -
Clinical Kidney Journal Dec 2023Hematuria-either macroscopic hematuria or asymptomatic microscopic hematuria-is a clinical feature typical but not specific for immunoglobulin A nephropathy (IgAN). The... (Review)
Review
Hematuria-either macroscopic hematuria or asymptomatic microscopic hematuria-is a clinical feature typical but not specific for immunoglobulin A nephropathy (IgAN). The only biomarker supported by the Kidney Disease: Improving Global Outcomes group as a predictor of progression, identifying patients needing treatment, is proteinuria >1 g/day persistent despite maximized supportive care. However, proteinuria can occur in the setting of active glomerulonephritis or secondary to sclerotic renal lesions. Microscopic hematuria is observed in experimental models of IgAN after IgA-IgG immunocomplex deposition, activation of inflammation and complement pathways. Oxidative damage, triggered by hemoglobin release, is thought to contribute to the development of proteinuria and progression. Despite being a clinical hallmark of IgAN and having a rational relationship with its pathophysiology, the value of microscopic hematuria in assessing activity and predicting outcomes in patients with IgAN is still debated. This was partly due to a lack of standardization and day-to-day variability of microhematuria, which discouraged the inclusion of microhematuria in large multicenter studies. More recently, several studies from Asia, Europe and the USA have highlighted the importance of microhematuria assessment over longitudinal follow-up, using a systematic approach with either experienced personnel or automated techniques. We report lights and shadows of microhematuria evaluation in IgAN, looking for evidence for a more consistent consensus on its value as a marker of clinical and histological activity, risk assessment and prediction of treatment response. We propose that hematuria should be included as part of the clinical decision-making process when considering when to use immunosuppressive therapy and as part of criteria for enrollment into clinical trials to test drugs targeting the inflammatory reaction elicited by immune pathway activation in IgAN.
PubMed: 38053974
DOI: 10.1093/ckj/sfad232 -
Clinical Pediatrics Dec 2023We aimed to evaluate the clinical parameters, histopathological findings of nephrotic syndrome (NS) patients, and independent factors predicting steroid resistance in a...
We aimed to evaluate the clinical parameters, histopathological findings of nephrotic syndrome (NS) patients, and independent factors predicting steroid resistance in a single tertiary center. One hundred and sixty-two children (57 girls and 105 boys) with NS who were followed between 1998 and 2018 were analyzed in this retrospective cohort. The median (interquartile range; range) age and follow-up time were 4.9 (5.7; 0.1-16.8) and 5.5 (5.4; 0.1-20.3) years. A total of 82.7% of the patients were steroid-sensitive nephrotic syndrome (SSNS) and 17.3% were steroid-resistant nephrotic syndrome (SRNS). The median age at first presentation was lower in the SSNS group ( = .002). The most common histopathological findings were focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Hypertension and macroscopic and microscopic hematuria were higher in the SRNS group ( < .001). The age and microscopic hematuria were independent risk factors for steroid resistance ( = .019 and = .002, respectively). Complement 3 (C3) was evaluated in 148 patients and found low in 7 patients who were subsequently diagnosed as membranoproliferative glomerulonephritis. There is still no better clinical predictor for steroid response than late age of onset and microscopic hematuria. Hypertension may also give a hint for potential steroid resistance.
PubMed: 38142361
DOI: 10.1177/00099228231219109 -
The Journal of Maternal-fetal &... Dec 2023Describe the clinical-surgical results of patients with PAS in the low-posterior cervical-trigonal space associated with fibrosis (PAS type 4) compared with PAS types in...
OBJECTIVE
Describe the clinical-surgical results of patients with PAS in the low-posterior cervical-trigonal space associated with fibrosis (PAS type 4) compared with PAS types in other locations (Types 1, upper bladder, 2 in upper parametrium) and in particular with PAS type 3, corresponding to dissectible cervical-trigonal invasion. The clinical-surgical results of using a standard hysterectomy were analyzed with a modified subtotal hysterectomy (MSTH) in patients with PAS type 4.
MATERIAL AND METHODS
A descriptive, retrospective, multicenter study included 337 patients of PAS; thirty-two corresponding to PAS type 4, from three PAS reference hospitals, CEMIC, Buenos Aires, Argentina, Fundación Valle de Lili, Cali, Colombia, and Dr. Soetomo General Hospital, Surabaya, Indonesia, between January 2015 and December 2020. PAS was diagnosed by abdominal and transvaginal ultrasound and topographically characterized by ultrafast T2 weighted MRI. In persistent macroscopic hematuria after MSTH, the surgeon performs an intentional cystotomy and uses a square compression suture to achieve the hemostasis inside the bladder wall.According to a PAS topographical classification, the patients with low-vesical cervical involvement compared with PAS located in relation with the upper blader (type1), upper parametrium (type 2 upper), and also with PAS situated in the lower vesical-trigon space (type 3). PAS 3 and 4 are located in identical area, but in type 3, group A, the vesicouterine space was dissectible, and in type 4, group B, significant fibrosis made surgical dissection extremely challenging. Furthermore, group B was divided into patients treated with total hysterectomy (HT) and those treated with a modified subtotal hysterectomy (MSTH). The surgical requirements to perform an MSHT included the availability of proximal vascular control at the aortic level (internal manual aortic compression, aortic endovascular balloon, aortic loop, or aortic cross-clamping). Then surgeon performed an upper segmental hysterotomy, avoiding the abnormal placenta invasion area; after that, the fetus was delivered, and the umbilical cord was ligated.After uterine exteriorization, the surgeon applies a continuous circular suture with number 2 polyglactin 910, taking some portions of the myometrium -to avoid unintentional slipping- around the lower uterine segment and a 3-4 cm proximal to the abnormal adhesion of the placenta. After tightening hard the circular suture, the uterine segment was circumferentially cut, three centimeters proximal to the circular hemostatic sutures. Next, the surgery follows the upper steps of conventional hysterectomy without changes. Additionally, the histological presence of fibrosis was examined in all samples.
RESULTS
Modified subtotal hysterectomy in patients with PAS type 4 (cervical-trigonal fibrosis) resulted in a significant clínico-surgical improvement over total hysterectomy. The median operative time and intraoperative bleeding were 140 min (IQR 90--240) and 1895 mL (IQR 1300-2500) in patients undergoing modified subtotal hysterectomy, and 260 min (IQR 210-287) and 2900 mL (IQR 2150-5500) in patients treated with total hysterectomy, respectively. The complication rate was 20% for MSHT and 82.3% for patients with a total hysterectomy.
CONCLUSIONS
PAS in the cervical trigonal area associated with fibrosis implies a greater risk of complications due to uncontrollable bleeding and organ damage. MSTH is associated with lower morbidity and difficulties in PAS type 4. Prenatal or intrasurgical diagnosis is essential to plan surgical alternatives to improve the results.
Topics: Pregnancy; Female; Humans; Placenta Accreta; Retrospective Studies; Uterus; Hysterectomy; Morbidity; Fibrosis; Placenta
PubMed: 37193605
DOI: 10.1080/14767058.2023.2183741 -
Pathophysiology : the Official Journal... Jul 2023Rats manifest a condition called hemorrhagic cystitis after spinal cord injury (SCI). The mechanism of this condition is unknown, but it is more severe in male rats than...
Rats manifest a condition called hemorrhagic cystitis after spinal cord injury (SCI). The mechanism of this condition is unknown, but it is more severe in male rats than in female rats. We assessed the role of sex regarding hemorrhagic cystitis and pathological chronic changes in the bladder. We analyzed the urine of male and female Sprague-Dawley and Fischer 344 rats after experimental spinal cord contusion, including unstained microscopic inspections of the urine, differential white blood cell counts colored by the Wright stain, and total leukocyte counts using fluorescent nuclear stains. We examined bladder histological changes in acute and chronic phases of SCI, using principal component analysis (PCA) and clustered heatmaps of Pearson correlation coefficients to interpret how measured variables correlated with each other. Male rats showed a distinct pattern of macroscopic hematuria after spinal cord injury. They had higher numbers of red blood cells with significantly more leukocytes and neutrophils than female rats, particularly hypersegmented neutrophils. The histological examination of the bladders revealed a distinct line of apoptotic umbrella cells and disrupted bladder vessels early after SCI and progressive pathological changes in multiple bladder layers in the chronic phase. Multivariate analyses indicated immune cell infiltration in the bladder, especially hypersegmented neutrophils, that correlated with red blood cell counts in male rats. Our study highlights a hitherto unreported sex difference of hematuria and pathological changes in males and females' bladders after SCI, suggesting an important role of immune cell infiltration, especially neutrophils, in SCI-induced hemorrhagic cystitis.
PubMed: 37489403
DOI: 10.3390/pathophysiology30030023 -
Kidney International Reports Aug 2023Macroscopic hematuria (MH) bouts, frequently accompanied by acute kidney injury (AKI-MH) are one of the most common presentations of IgA nephropathy (IgAN) in the...
INTRODUCTION
Macroscopic hematuria (MH) bouts, frequently accompanied by acute kidney injury (AKI-MH) are one of the most common presentations of IgA nephropathy (IgAN) in the elderly. Immunosuppressive therapies are used in clinical practice; however, no studies have analyzed their efficacy on kidney outcomes.
METHODS
This is a retrospective, multicenter study of a cohort of patients aged ≥50 years with biopsy-proven IgAN presenting with AKI-MH. Outcomes were complete, partial, or no recovery of kidney function at 1 year after AKI-MH, and kidney survival at 1, 2, and 5 years. Propensity score matching (PSM) analysis was applied to balance baseline differences between patients treated with immunosuppression and those not treated with immunosuppression.
RESULTS
The study group consisted of 91 patients with a mean age of 65 ± 15 years, with a mean follow-up of 59 ± 36 months. Intratubular red blood cell (RBC) casts and acute tubular necrosis were found in all kidney biopsies. The frequency of endocapillary hypercellularity and crescents were low. Immunosuppressive therapies (corticosteroids alone or combined with mycophenolate mofetil or cyclophosphamide) were prescribed in 52 (57%) patients, whereas 39 (43%) received conservative treatment. There were no significant differences in the proportion of patients with complete, partial, or no recovery of kidney function at 1 year between patients treated with immunosuppression and those not treated with immunosuppression (29% vs. 36%, 30.8% vs. 20.5% and 40.4 % vs. 43.6%, respectively). Kidney survival at 1, 3, and 5 years was similar among treated and untreated patients (85% vs. 81%, 77% vs. 76% and 72% vs. 66%, respectively). Despite the PSM analysis, no significant differences were observed in kidney survival between the two groups. Fourteen patients (27%) treated with immunosuppression had serious adverse events.
CONCLUSIONS
Immunosuppressive treatments do not modify the unfavorable prognosis of patients with IgAN who are aged ≥50 years presenting with AKI-MH, and are frequently associated with severe complications.
PubMed: 37547537
DOI: 10.1016/j.ekir.2023.05.027 -
Nefrologia 2023
Topics: Humans; Glomerulonephritis, IGA; Hematuria; Proteinuria
PubMed: 37914637
DOI: 10.1016/j.nefroe.2023.10.003 -
Pediatric Nephrology (Berlin, Germany) Mar 2024Tubulointerstitial lesions and glomerular inflammation severity have been shown to correlate with proteinuria in children with IgA nephropathy (cIgAN). However, there is...
BACKGROUND
Tubulointerstitial lesions and glomerular inflammation severity have been shown to correlate with proteinuria in children with IgA nephropathy (cIgAN). However, there is a lack of data regarding severity of histopathologic findings in cIgAN in patients with minimal to absent proteinuria since kidney biopsy indications are not well defined in these cases.
METHODS
Twenty-eight cIgAN patients with kidney biopsy from 4 different centers in Paris (France) and Montreal (Canada) with a urine protein/creatinine ratio (UPCr) ≤ 0.03 g/mmol and a normal estimated glomerular filtration rate (eGFR > 90 ml/min/1.73 m) on the day of kidney biopsy prior to treatment were included.
RESULTS
Median age was 11.82 (9.32-13.45) years, and median follow-up was 4 years (2.87-6.53). At time of biopsy, median eGFR was 116 (102.3-139.7) ml/min/1.73 m, and median UPCr was 0.02 (0.011-0.03) g/mmol. Microscopic or macroscopic hematuria was present in 35.7% and 64.3% of cases, respectively. Kidney biopsy microscopy analysis showed mesangial (M1), endocapillary (E1), or extracapillary (C1) hypercellularity in 53.5%, 32.1%, and 7.1% of patients, respectively. Chronic histological lesions were also present: glomerulosclerosis (S1) in 42.8% and tubular atrophy/interstitial fibrosis in 7.1%. Podocytopathic features were detected in 21.4%. An ACE inhibitor or immunosuppressive therapy (IS) was prescribed in 42.8% and 21.4% of these patients respectively. One-third (35.7%) received no treatment. At last follow-up, median eGFR was 111.9 (90.47-136.1) ml/min/1.73 m, and median UPCr was 0.028 (0.01-0.03) g/mmol.
CONCLUSION
cIgAN with minimal proteinuria at time of biopsy might be linked with acute and chronic glomerular lesions.
Topics: Child; Humans; Biopsy; Glomerular Filtration Rate; Glomerular Mesangium; Glomerulonephritis, IGA; Kidney; Kidney Glomerulus; Proteinuria; Retrospective Studies; Adolescent
PubMed: 37698655
DOI: 10.1007/s00467-023-06121-7 -
Cureus Aug 2023The association between Klippel-Trenauney syndrome (KTS) and bladder hemangiomas is rare. The most common clinical manifestation is hematuria. The diagnosis is made from...
The association between Klippel-Trenauney syndrome (KTS) and bladder hemangiomas is rare. The most common clinical manifestation is hematuria. The diagnosis is made from the characteristic cystoscopic appearance of the tumor. We report the case of a patient presenting recurrent macroscopic hematuria in the context of KTS. A cystoscopic evaluation revealed bladder hemangiomas. A conservative approach consisting of bladder irrigation and close follow-up was chosen as therapy. Conservative treatment of bladder irrigation and close follow-up is the recommended initial treatment of moderate and infrequent episodes of hematuria in this context. The more invasive therapeutic options have to be considered especially for frequent or life-threatening episodes of hematuria. This case suggests that conservative treatment may be effective in treating moderate and infrequent episodes of hematuria due to bladder hemangioma in the context of KTS. Further studies are required to adequately establish the effectiveness, limitations, and complications of each approach.
PubMed: 37664271
DOI: 10.7759/cureus.42797