Intrarenal Disease Research Articles

Diagnosing Polyomavirus Nephropathy without a Biopsy: Validation of the Urinary PyV-Haufen-Test in a Proof-of-Concept Study including Uromodulin Knock-out-Mice.

Polyomavirus nephropathy (PyVN) leads to kidney transplant dysfunction and loss. Since a definitive diagnosis requires an invasive kidney biopsy, a timely diagnosis is often hampered. In this clinical dilemma the PyV-haufen-test, centering around the detection of three-dimensional PyV aggregates in the urine, might provide crucial diagnostic information. A multistep experimental design. Hypothesis: PyV-haufen form within the kidneys under high concentrations of uromodulin, a kidney specific protein; PyV-haufen are kidney-specific-disease-markers. Investigative step A showed colocalization of uromodulin with aggregated PyV (i) in ten kidneys with PyVN by immunohistochemistry, (ii) in urine samples containing PyV-haufen by electron microscopy/immunogold labeling (n = 3), and (iii) in urine samples containing PyV-haufen by immunoprecipitation assays (n = 4). Investigative step B: In in-vitro experiments only high uromodulin concentrations of ≥ 1.25 mg/mL aggregated PyV, as is expected to occur within injured nephrons. In contrast, in voided urine samples (n = 59) uromodulin concentrations were below aggregation concentrations (1.2 -19.6 µg/mL). Investigative step C: 0/11 (0%) uromodulin KO-/- mice with histologic signs of PyVN showed urinary PyV-haufen shedding compared to 10/14 (71%) WT+/+ mice. PyV-haufen form within kidneys under high uromodulin concentrations. Thus, PyV-haufen detected in the urine are specific biomarkers for intra-renal disease, i.e. definitive PyVN.

The Role of Vascular Lesions in Diabetes Across a Spectrum of Clinical Kidney Disease

IntroductionThe clinical-histologic correlation in diabetic nephropathy is not completely known.MethodsWe analyzed nephrectomy specimens from 90 patients with diabetes and diverse degrees of proteinuria and glomerular filtration rate (GFR).ResultsThirty-six (40%) subjects had normoalbuminuria, 33 (37%) microalbuminuria, and 21 (23%) non-nephrotic proteinuria. Mean estimated GFR (eGFR) was 65±23 (40% <60 ml/min per 1.73 m2). About 170 glomeruli per patient were analyzed, and all samples included vascular tissue. Six subjects (7%) were classified in diabetic nephropathy class I, 61 (68%) in class II-a, 13 (14%) in class II-b, 9 (10%) class III, and 1 (1%) in class IV. Eighty percent to 90% of those with normoalbuminuria or microalbuminuria were classified in class II-a or II-b and <10% in class III; 52% of those with proteinuria were in class II-a, 15% in class II-b, and 19% in class III. Nodular sclerosis (57%) and mesangial expansion (15%) were more frequent in cases with proteinuria than in normoalbuminuria (28% and 8%; P = 0.028 and 0.017). About 20% to 30% of all cases, regardless the level of albuminuria or proteinuria or the histologic class had tubular atrophy, interstitial fibrosis, or inflammation in >10% to 20% of the sample. Moderate hyalinosis and arteriolar sclerosis were observed in 80% to 100% of cases with normoalbuminuria, microalbuminuria, proteinuria, as well as in class I, II, or III.ConclusionsWeak correspondence between analytical parameters and kidney histology was found. Thus, disease may progress undetected from the early clinical stages of the disease. Finally, vascular damage was a very common finding, which highlights the role of ischemic intrarenal disease in diabetes.

Angioplasty for renovascular hypertension in 78 children

ObjectivesTo evaluate the outcome of percutaneous transluminal angioplasty (PTA) in children with renovascular hypertension (RVH) treated at a single centre over 29 years.MethodsA retrospective study of the medical charts of...

Pre- and postcaptopril renal scintigraphy as a screening test for renovascular hypertension in children

We studied the ability of pre- and postcaptopril renal scintigraphy to predict renovascular disease (RVD) in children. Retrospective review of medical notes and radiology reports of all hypertensive children who had had both pre- and postcaptopril renal scintigraphy with [(99m)Tc] dimercaptosuccinic acid (DMSA) and/or [(99m)Tc] mercaptoacetyltriglycine (MAG3) and digital subtraction angiography (DSA). 81 children aged 1-18 (median 10) years were studied with 62% (51) having a diagnosis of RVD. Main renal artery disease, intrarenal disease, and both main and intrarenal artery disease were present in 25, 14, and 12 patients respectively. The isotope study accurately diagnosed RVD, confirmed by DSA, in 47% (24 of 51) children, with eight false positive studies. The sensitivity, specificity, and positive and negative predictive values of the isotope study to predict RVD were 48%, 73%, 76%, and 51%, respectively. Pre- and postcaptopril renal scintigraphy was unable to predict RVD in children.

Results of surgical treatment for renovascular hypertension in children: 30 year single centre experience

We retrospectively reviewed the medical records of all patients who underwent surgery as part of the treatment of renovascular hypertension (RVH) at our centre between 1979 and 2008. Patients. Thirty-seven children (65% male) with a median age of 7.6 (0.4-17.9) years were identified with a median systolic blood pressure (SBP) of 140 (105-300) mm Hg prior to surgery. Bilateral renal artery stenosis and intra-renal disease were present in 19 (51%) patients, mid-aortic syndrome in 15 (40%), involvement of visceral arteries in eight out of 35 (23%) and coexisting cerebral disease in eight out of 30 (26%) investigated patients. Surgical procedures (n = 53) included (i) nephrectomy (18, of which two unplanned and two secondary due to technical failure), (ii) renovascular surgery on the renal arteries (28, of which 18 had autologous surgery and 10 synthetic grafts inserted for revascularisation) and (iii) aortic reconstruction with (6) and without (1) a synthetic graft. Post-operative complications were haemorrhage (5), septicaemia (5) and chylous ascites (1). There were no perioperative deaths; two children died during follow-up. The SBP post-surgery improved to a median value of 116 (range 90-160) mm Hg. Twelve months after surgery, 16 (43%) children had normal blood pressure without treatment, 15 (41%) normal or improved on one to four antihypertensive drugs and four (11%) unchanged; no data were available for two (5%) children. Surgery effectively treated the hypertension of 90% of our children, when performed in conjunction with medical therapy and interventional radiology. In spite of aggressive surgical treatment, RVH is sometimes a progressive disease.

Angioplasty for Renovascular Hypertension in Children: 20-Year Experience

Our aim was to evaluate the clinical outcomes, safety, and efficacy of percutaneous transluminal angioplasty for renovascular hypertension in children. A retrospective review of data for all children with renovascular hypertension who underwent percutaneous transluminal angioplasty at a single center between 1984 and 2003 was performed. Patients with renal transplants and inflammatory multisystem diseases were excluded. Thirty-three children, 1.9 to 17.9 years of age (median: 10.3 years), underwent renal angioplasty and/or stenting. Underlying syndromes were present in 10. On angiograms, 16 had bilateral renal artery stenosis, 15 intrarenal disease, 8 aortic stenosis, and 7 cerebrovascular disease. Forty-eight percutaneous transluminal angioplasty procedures were performed, including 15 stenting procedures. There was a high rate of restenosis after stenting (7 of 19 cases, compared with 2 of 27 cases after balloon dilation). Outcomes were cured (ie, blood pressure normal without treatment) for 9 patients, improved blood pressure with same or reduced treatment for 7, blood pressure maintained in >95th percentile because of cerebrovascular disease for 2, no change in blood pressure despite technical success for 10, and technical failure for 5. Blood pressure control improved in 11 of 13 children who had main renal artery disease alone and in 6 of 20 with associated intrarenal disease or stenoses in other vascular beds. There was 1 procedure-related death and 5 minor complications. Angioplasty produced clinically worthwhile improvement for approximately 50% of patients. High incidence rates of extrarenal involvement and intrarenal disease and a high restenosis rate after stenting accounted for poor blood pressure control in the rest.

Variables preoperatorias pronóticas en el cáncer de riñón

To analyze the correlation between preoperative variables in patients with kidney cancer and subsequent finding of bad prognosis factors. Retrospective cohort study reviewing the charts of all patients undergoing surgery at the HIBA bet- ween June 1988 and April 2003. 555 patients were included, registering age, gender, and clinical presentation. Pathology reports were classified following WHO for histology, Furhman for tumor grade, and AJCC for tumor stage. Intrarenal disease was defined as tumors < or = T2; the rest of the tumors were considered extrarenal. Statistical analysis was performed using the Statistic 7 Software, performing Students t test, proportions comparison test, chi-square test, and odds ratio. Mean age was 58.8 years (r: 20-94), 388 (69.9%) patients were males and 167 (30.1%) females. 209 (37.7%) were smokers or ex-smokers. 256 (46.1%) tumors were incidentally diagnosed, 299 (53.9%) were symptomatic. The right kidney was affected more often (54.6%), and 2.3% were bilateral synchronic tumors. Grade II was the most frequent grade (62.2%). T1 was the predominant TNM with 273 patients (49.2%). Mean tumor size was 6.7 cm, with 5.54 cm for the intrarenal tumors and 8.67 cm for the extrarenal (Student t test p < 0.00001). 49.6% (127) of the 256 asymptomatic patients have extrarenal tumors, in comparison with only 26.4% (79) of the 299 symptomatic patients (chi-square p < 0.00001). Ninety-two (44%) of the 209 smokers had extrarenal tumors in comparison with 114 (32.9%) of the non-smokers. We may say that patients having a symptomatic renal tumor have between 2 and 3 times more probability to have non organ-confined disease at the time of surgery This also increases, although in smaller amounts, between smokers and older than 70 years patients. The presence of a tumor greater than 7 cm almost triplicates of the possibility of extrarenal involvement.

Acute Renal Failure Due to Intrinsic Renal Diseases: Review of 1122 Cases

In this study we have analyzed incidence, causes and clinical course of ARF due to primary intrarenal disease other than acute tubular necrosis. Thousand hundred and twenty two cases of ARF of diverse etiology were studied over a period of 16 years; 07 1984 to Dec, 1999. Surgical ARF 231 (20.6%) were not included in the present study. Intrinsic renal diseases were responsible for ARF in 891 (79.4%) of cases. The most common intrinsic renal diseases 705 (79.4%) causing ARF were ischemic/toxic acute tubular necrosis, but not included in this study. Acute renal failure was related to acute glomerulonephritis (9.3%), acute interstitial nephritis (7%), and renal cortical necrosis in (4.6%) of cases. Therefore intrinsic renal diseases other than ATN were the causative factor for acute renal failure in 186 (20.8%) patients in our study. Crescentic (51.8%) and endocapillary proliferative glomerulonephritis (34.9%), were the main glomerular diseases responsible for ARF and 75.9% of GN was related to infectious etiology. Fifty three percent of acute interstitial nephritis was drug induced and in 25 (40%) patients it was related to an infectious etiology. Renal cortical necrosis due to HUS was observed in 16 (39%) children and majority (76.47%) of the cases had a diarrhoeal prodrome. Obstetrical complications were the main causes (61%) of cortical necrosis in adults with acute renal failure. Thus, intrinsic renal diseases other than ATN were responsible for ARF in 186 (20.8%) cases. Post-infectious glomerulonephritis, acute interstitial nephritis and renal cortical necrosis (complicating HUS in children and obstetrical complications in adult) are the main causes of acute renal failure in our study. Both acute GN and interstitial nephritis had excellent prognosis, however renal cortical necrosis was associated with a very high mortality.

Local staging of Wilms' tumor—computerized tomography correlation with histological findings

Purpose: The aim of this study was to assess the accuracy of computed tomography (CT) in the local staging of Wilms' tumor. Methods: Twenty-six patients with unilateral, nonmetastatic Wilms' tumors were accrued over the period of 1990 through 1997. Preoperative CT staging was performed before surgical biopsy or excision. The abdominal CT images were reviewed and staged for local disease according to National Wilms' Tumour Study (NWTS) Group Staging V as either intrarenal disease (Stage I), local extrarenal extension amenable to complete local excision (Stage II), or advanced local disease (Stage III). Patients with metastatic (Stage IV) and bilateral disease (Stage V) were excluded from our study. Results were compared to histological findings. Results: CT scan correctly staged 10 of 26 cases (38%) of Wilms' tumor. CT scan overstaged 12 of 16 (75%) localized renal disease (Stage I) and local extension (Stage II) tumors, and understaged 4 of 10 (40%) localized spread (Stage III) tumors. Conclusions: CT scan appears to have poor correlation to histological staging. Therefore, basing therapy solely on radiological imaging may lead to some patients receiving more intense therapy than necessary, whereas others do not receive sufficient therapeutic regimens. Histological assessment of the excised mass should remain the standard for staging Wilms' tumors. J Pediatr Surg 35:677-679. Copyright © 2000 by W.B. Saunders Company.

Can intrarenal duplex waveform analysis predict successful renal artery revascularizaion?

Purpose: No currently available noninvasive test can preoperatively predict a successful outcome to renal revascularization. Resistance measurements from the renal parenchyma obtained with duplex sonography reflect the magnitude of intraparenchymal disease, and patients with extensive intrarenal disease may respond less favorably to revascularization. To address this question, we reviewed our (primarily) operative experience in patients undergoing renal artery revascularization, and compared the blood pressure (BP) and renal function response with resistance measurements obtained from the kidney both before and after revascularization. Methods: During a 56-month period, 31 consecutive renal artery revascularizations (25 surgical and 6 percutaneous angioplasties) were performed in 23 patients (21 atherosclerotic, 2 fibromuscular dysplasia). Duplex sonography was performed in each patient before and after revascularization, and parenchymal diastolic/systolic (d/s) ratios were calculated. BP and renal function response to intervention were compared with measurements of intrarenal flow patterns before and after revascularization. Results: Mean parenchymal peak systolic velocity was significantly higher after repair in all patients (pre-repair: 19.5 ± 1.3, postrepair: 27.2 ± 1.7; P<.0001). Despite this, there were no statistical differences between preoperative and postoperative parenchymal d/s ratios. A favorable (cured or improved) BP response was seen in 81% (17 of 21) of revascularizations performed for hypertension. Among these successes, parenchymal d/s ratios were in the normal range (ie, ≥0.30) both before and after repair (mean pre-repair: 0.34 ± 0.03, mean postrepair: 0.31 ± 0.03; not significant). In 4 patients in which BP failed to improve after intervention, the d/s ratio was abnormal before surgery (<0.3), and remained so after revascularization (mean preoperative d/s ratio: 0.18 ± 0.04, mean postoperative d/s ratio: 0.11 ± 0.04; P = .003). Mean preoperative parenchymal d/s ratios were significantly higher in all patients with a successful BP response when compared with failures ( P = .048). Similarly, among patients with single artery repairs, mean preoperative d/s ratios approached significance in successes vs. failures (success: 0.40 ± 0.03, failure: 0.21 ± 0.03; P = .054). A decrease in serum creatinine greater than or equal to 20% was seen in 8 of 18 patients (44%) with ischemic nephropathy. These patients also had normal d/s ratios preoperatively (mean 0.39 ± 0.04), whereas the 10 patients who failed to improve had significantly lower ratios (mean 0.24 ± 0.03; P = .041). Kidney length did not correlate with d/s ratio. Conclusion: Although we do not believe that duplex sonographic measurement of intrarenal flow patterns alone is an accurate means of assessing main renal artery occlusive disease, the resistive indices seem to reflect the magnitude of intraparenchymal disease, and thus may provide important prognostic information for patients undergoing surgical revascularization. Our data suggest that a preoperative d/s ratio below 0.3 correlates with clinical failure relative to BP and renal function responses. (J Vasc Surg 1998;28:471-81.)

Plasma Renin Activity in Renal Transplant Patients With Hypertension

Chronic renal allograft rejection (CR) is the major cause of graft loss after 1 year following transplantation. Hypertension (HTN) and proteinuria (Up) are the hallmarks of this immunologic allograft response. Over 1 year, 23 patients posttransplantation and with HTN (diastolic greater than 95 mm Hg) were examined. Serial serum creatinine (Scr), Up, urine creatinine (Ucr), and resting and enalapril challenged (EC) plasma renin activity (PRA) were all determined. Renal artery stenosis was excluded by noninvasive imaging. Of the 23 patients, eight eventually lost their renal allografts, while 15 maintained satisfactory renal function (Scr less than 2.5). Results of this study show that: 1) worsening renal function (RF) increases EC reactivity; 2) the presence of proteinuria is not itself related to increase in EC activity; 3) renin before and after EC was higher (P = .06) in the allograft loss group. In this study, patients with high PRA represent the highest EC responses. Therefore, they display not macrovascular lesions, but microvascular intrarenal disease; this defect is most likely secondary to chronic immunologic insult.

Differentiation of renal from non-renal hematuria by microscopic examination of erythrocytes in urine.

Recent studies indicate that hematuria of renal parenchymal origin can be differentiated from hematuria of other origin by the presence of dysmorphic urinary erythrocytes (cells exhibiting irregular membranes or small surface blebs). We investigated the utility of this simple screening assay in a routine clinical laboratory. Dysmorphic erythrocytes in urine from 69 patients (18 with renal-parenchymal disease) were quantified on unstained slides by medical technologists using phase-contrast microscopes. Samples stored at 4 degrees C or 23 degrees C for up to 5 h had no significant changes in percentages of dysmorphic erythrocytes (PDE). PDE was also not modified by urea nitrogen concentration, osmolality, or pH over the physiological ranges of these variables. Receiver-operating characteristic (ROC) curves indicated an optimal sensitivity of 88% and specifity of 94% at a decision level of 14% dysmorphic erythrocytes per high-power field. Thus, the presence of fewer than 14% dysmorphic cells is suggestive of extra-renal disease; more than 14% is suggestive of intra-renal disease.

Surgical Correction of Intrarenal Disease. I. Obstructions of the Superior Infundibulum

Surgical Correction of Intrarenal Disease. I. Obstructions of the Superior Infundibulum

The Diagnosis of Reversible Renal Hypertension.

Excerpt The renal origin of hypertension is well established in cases of main renal artery stenosis or unilateral intra-renal disease. Surgical repair of diseased renal arteries or unilateral nephr...