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A 28-year-old woman with a 5-year history of untreated hypertension was admitted for respiratory distress, hemoptysis, and retinopathy. Computed tomography showed diffuse plaques in both lung fields. Acute kidney injury, hemolytic anemia, and thrombocytopenia were noted. Kidney biopsy showed thrombosis with fibrinoid necrosis and edematous intimal thickening and luminal narrowing of the small renal artery, indicating thrombotic microangiopathy; the majority of glomeruli were collapsed. After 8 weeks of treatment with antihypertensive drugs, serum creatinine decreased to 1.0 mg/dL, and the patient recovered. In the absence of any other underlying disease, malignant nephrosclerosis associated with a hypertensive emergency was diagnosed., Competing Interests: Declarations. Conflict of interest: The authors declare no competing financial interests and no conflicts of interest. Ethical approval: The present study adhered to the Declaration of Helsinki, and the patient gave her consent for the case report to be published., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Nephroangiosclerosis or kidney disease that accompanies chronic essential arterial hypertension has been known for more than a hundred years. The definitive diagnosis is established by renal biopsy, which is reserved for doubtful cases or atypical presentation, being in most cases a presumptive clinical diagnosis. The objective of this review is to analyse the main controversies that currently exist related to nephroangiosclerosis: inaccuracy in epidemiological aspects (prevalence and incidence unknown), diagnostic difficulties and lack of correlation studies between clinical data and histopathology, progression factors in Caucasians. Currently, with advances in genetic studies in hypertension, not using or redefining the term hypertensive kidney disease for another condition such as nephropathy related to the present genetic alteration is being considered., (Copyright © 2022 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

A 37-year-old Japanese man was admitted to our hospital for evaluation of severe hypertension and visual impairment. His serum creatinine was 4.16 mg/dL. Plasma renin activity was normal (2.7 ng/mL/h), but plasma aldosterone concentration was elevated (27.2 ng/dL). A kidney biopsy showed concentric subendothelial edematous thickening of the arterioles (onion skin pattern) with luminal narrowing or obstruction, and malignant nephrosclerosis was diagnosed. Antihypertensive therapies, including an angiotensin II receptor blocker and spironolactone, were administered and effectively preserved kidney function and normalized blood pressure. This case indicates that hyperaldosteronemia in the presence of normal renin levels might also cause malignant hypertension., (© 2022. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

Background: Hypertensive nephrosclerosis is the presumed underlying cause in many end-stage kidney disease (ESKD) patients, but the diagnosis is disputed and based on clinical criteria with low diagnostic accuracy., Objective: To evaluate and improve the diagnostic process for nephrosclerosis patients., Methods: We included adults from the population-based HUNT study (n = 50 552), Norwegian CKD patients referred for kidney biopsy 1988-2012 (n = 7261), and unselected nephrology clinic patients (n = 193) used for matching. Decision tree analysis and ROC curve-based methods of optimal cut-offs were used to improve clinical nephrosclerosis criteria., Results: Nephrosclerosis prevalence was 2.7% in the general population, and eGFR decline and risk for kidney-related hospital admissions and ESKD were comparable to patients with diabetic kidney disease. In the biopsy cohort, current clinical criteria had very low sensitivity (0.13) but high specificity (0.94) for biopsy-verified arterionephrosclerosis. A new optimized diagnostic algorithm based on proteinuria (<0.75 g d -1 ), systolic blood pressure (>155 mm Hg) and age (>75 years) only marginally improved diagnostic accuracy (sensitivity 0.19, specificity 0.96). Likewise, there were still false-positive cases with treatable diagnoses like glomerulonephritis, interstitial nephritis and others (40% of all test positive). Decision curve analysis showed that the new criteria can lead to higher clinical utility, especially for patients considering the potential harms to be close to the potential benefits, while the more risk-tolerant ones (harm:benefit ratio < 1:4) should consider kidney biopsy., Conclusion: Further improvements of the current clinical criteria seem difficult, so risks and benefits of kidney biopsy could be more actively discussed with selected patients to reduce misclassification and direct treatment., (© 2020 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

A 31-year-old woman with retinitis pigmentosa who had been diagnosed with renal failure due to nephrosclerosis related to hypertensive disorders of pregnancy was referred to our hospital to prepare for renal replacement therapy. Ultrasonography and MRI of the kidneys revealed multiple corticomedullary cysts. A renal biopsy showed that the tubules were tortuous and atrophic with segmented tubular basement membrane thickening. These findings indicated that she had Senior-Løken syndrome. A molecular genetic analysis was performed, and homozygous deletion of the gene encoding nephronophthisis-1 was found. Thus, the clinical diagnosis of Senior-Løken syndrome was genetically confirmed. Because her renal function was gradually worsening, she was scheduled to undergo living donor kidney transplantation. Senior-Løken syndrome, which is recognised as a very rare paediatric inherited disease characterised by nephronophthisis and eye problems, can cause adult-onset end-stage renal failure., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: An overweight person is at high risk for hypertensive renal damage. The effect of weight on the association between systolic blood pressure (SBP) and albuminuria remains unknown in patients with histologically diagnosed hypertensive nephrosclerosis., Methods: A total of 97 patients with biopsy-confirmed hypertensive nephrosclerosis were recruited from 13 centers throughout Japan. We examined the relationship between SBP and proteinuria among those who were overweight, which is defined as a body mass index ≥25 kg/m2, and those who were not. We examined the interaction of weight and SBP with albuminuria at baseline and with the changes in estimated glomerular filtration rate (eGFR) during the observational period., Results: Our results included mean age (54 years old), blood pressure (138/80), eGFR (53 ml/min/1.73 m2), and urine albumin levels (0.2 g/day). SBP was significantly correlated with log-transformed urine albumin levels (r = 0.4, P = 0.01) in patients who were overweight (n = 38) compared with patients who were not overweight (n = 59). Multiple regression analysis revealed that the interaction between being overweight and SBP with respect to albuminuria was significantly correlated with the log-transformed urine albumin level (β = 0.39, P = 0.047) and was independent of age, sex, and potential confounding factors. The interaction between weight and SBP ≥140 mm Hg was significantly associated with a greater decrease in eGFR in the following 3 years., Conclusions: Being overweight may enhance susceptibility to hypertensive glomerular damage and may eventually lead to renal progression in patients with hypertensive nephrosclerosis., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aim: The influence of serum urate on kidney disease is attracting attention, but the effects of uric acid (UA) on nephrosclerosis have not been elucidated., Methods: We reviewed data from 45 patients diagnosed with arterial/arteriolar nephrosclerosis. The renal outcomes of the arterial/arteriolar nephrosclerosis patients were assessed by performing logistic and Cox regression analyses. A Kaplan-Meier analysis was used to evaluate the impact of hyperuricemia (HU) on kidney survival. The renal outcomes of patients with and without HU were compared by using a propensity score-matched cohort., Results: The logistic regression models showed no significant differences in renal outcomes, according to baseline parameters or follow-up parameters, except the serum UA value and body mass index (BMI). Baseline serum UA level had the highest odds ratio (OR) for estimated glomerular filtration rate (eGFR) decline (OR, 1.86; 95% confidence interval (CI), 1.12 to 3.45), among the parameters assessed. In the multivariate Cox regression analysis, HU (UA ≥8.0 mg/dL) (P=0.01) and BMI (P=0.03) were significantly associated with a ≥50% eGFR decline or ESRD. The Kaplan-Meier analysis in the propensity score-matched cohort indicated that the renal survival rate of the group of arterial/arteriolar nephrosclerosis patients with HU was significantly lower than that of the group without HU (log rank, P=0.03)., Conclusion: The results of this study suggest that the baseline serum UA value can serve as a renal outcome predictor in arterial/arteriolar nephrosclerosis patients.

All forms of progressive renal diseases develop a final pathway of tubulointerstitial fibrosis and glomerulosclerosis. Renal fibrosis is usually quantified using histological staining, a process that is time-consuming and pathologist dependent. Here we develop a fast and operator-independent method to measure fibrosis utilizing the murine unilateral ureteral obstruction model which manifests a time-dependent fibrotic increase in obstructed kidneys while the contralateral kidneys are used as controls. After ureteral obstruction, kidneys were analyzed at 7, 14, and 21 days. Fibrosis was quantified using fluorescence lifetime imaging (FLIM) and second harmonic generation (SHG) in a Deep Imaging via Enhanced photon Recovery deep tissue imaging microscope. This microscope was developed for deep tissue along with second and third harmonic generation imaging and has extraordinary sensitivity toward harmonic generation. SHG data suggest the presence of more fibrillar collagen in the obstructed kidneys. The combination of short-wavelength FLIM and SHG analysis results in a robust assessment procedure independent of observer interpretation and let us create criteria to quantify the extent of fibrosis directly from the image. Thus, the FLIM-SHG technique shows remarkable improvement in quantification of renal fibrosis compared to standard histological techniques., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Even among ostensibly healthy adults, there is often mild pathology in the kidney. The detection of kidney microstructural variation and pathology by imaging and the clinical pattern associated with these structural findings is unclear., Study Design: Cross-sectional (clinical-pathologic correlation)., Setting & Participants: Living kidney donors at Mayo Clinic (Minnesota and Arizona sites) and Cleveland Clinic 2000 to 2011., Predictors: Predonation kidney function, risk factors, and contrast computed tomographic scan of the kidneys. These scans were segmented for cortical volume and medullary volume, reviewed for parenchymal cysts, and scored for kidney surface roughness., Outcomes: Nephrosclerosis (glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis) and nephron size (glomerular volume, mean profile tubular area, and cortical volume per glomerulus) determined from an implantation biopsy of the kidney cortex at donation., Results: Among 1,520 living kidney donors, nephrosclerosis associated with increased kidney surface roughness, cysts, and smaller cortical to medullary volume ratio. Larger nephron size (nephron hypertrophy) associated with larger cortical volume. Nephron hypertrophy and larger cortical volume associated with higher systolic blood pressure, glomerular filtration rate, and urine albumin excretion; larger body mass index; higher serum uric acid level; and family history of end-stage renal disease. Both nephron hypertrophy and nephrosclerosis associated with older age and mild hypertension. The net effect of both nephron hypertrophy and nephrosclerosis associating with cortical volume was that nephron hypertrophy diminished volume loss with age-related nephrosclerosis and fully negated volume loss with mild hypertension-related nephrosclerosis., Limitations: Kidney donors are selected on health, restricting the spectrum of pathologic findings. Kidney biopsies in living donors are a small tissue sample leading to imprecise estimates of structural findings., Conclusions: Among apparently healthy adults, the microstructural findings of nephron hypertrophy and nephrosclerosis differ in their associations with kidney function, macrostructure, and risk factors., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Kidney biopsies are not routinely performed for diabetic patients with chronic kidney disease. However in some cases, a biopsy is carried out to exclude other treatable Prolonged duration of diabetes, insulin therapies and presence of diabetic retinopathy were associated with a greater likelihood of DN. The high prevalence of NDRD in our population emphasizes the judicious use of kidney biopsy in diabetic patients. e renal diseases. The prevalence and the nature of non diabetic renal disease (NDRD) among diabetic patients in Israel have not yet been evaluated., Objective: To assess pathological findings of kidney biopsies conducted in patients with diabetes mellitus., Methods: A total of 200 native kidney biopsies were performed during the study period. Patients who had a diagnosis of diabetes mellitus were included in the study. Clinical data and pathological findings were retrospectively collected and analyzed., Results: The cohort included 34 patients, median age 61.8 years. The male to female ratio was 25:9; mean serum creatinine was 1.8 ± 1.2 mg/dl The duration of diabetes was significantly shorter in patients with NDRD (6.8 ± 7.1 years vs. 13.0 ± 9.6 years in diabetic nephropathy (DN) or combined), whereas insulin therapy was significantly more common in patients with DN (72% vs 5% in NDRD). Diabetic retinopathy was documented in 57% of patients with diabetic nephropathy but wasn't documented in any patient with NDRD. Prevalence of NDRD, DN and combined pathology was 58.8%, 32.4% and 8.8% respectively. Neither the level of proteinuria nor the rate of renal function deterioration could predict pathological findings in the biopsy. The most common NDRD disease was nephrosclerosis., Conclusions: Non-diabetic renal disease was common. Prolonged duration of diabetes, insulin therapies and presence of diabetic retinopathy were associated with a greater likelihood of DN. The high prevalence of NDRD in our population emphasizes the judicious use of kidney biopsy in diabetic patients.

Despite a growing organ shortage in the United States, many deceased donor kidneys removed for transplantation are discarded. Kidney biopsy findings often play a role in these discards, although it is not clear whether biopsies reliably inform acceptance decisions. Therefore, we carried out a systematic review of the medical literature on the utility of both procurement and implantation biopsies for predicting posttransplant outcomes. Between January 1, 1994 and July 1, 2014, 47 studies were published in the English language literature that examined the association between pretransplant donor biopsy findings from 50 or more donors (with more than half being from deceased donors) and either posttransplant graft failure, delayed graft function, or graft function. In general, study quality was poor. All were retrospective or did not indicate if they were prospective. Results were heterogeneous, with authors as often as not concluding that biopsy results did not predict posttransplant outcomes. The percent glomerular sclerosis was most often examined, and failed to predict graft failure in 7 of 14 studies. Of 15 semiquantitative scoring systems proposed, none consistently predicted posttransplant outcomes across studies. Routine use of biopsies to help determine whether or not to transplant a kidney should be reexamined., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Nephrosclerosis progresses slowly to end-stage renal disease (ESRD) in only a small percentage of patients. However, because hypertension and nephrosclerosis are normally found simultaneously, nephrosclerosis is a risk factor for cardiovascular disease (CVD). In turn, the onset of CVD may progress to further renal impairment., Aim: To evaluate clinical outcomes and the association between nephrosclerosis and CVD in the long term., Design: Prospective study, Methods: We prospectively assessed 35 patients (male/female: 19/16) with nephrosclerosis aged >30 years at disease onset, attending the Kidney Disease Center, Saitama Medical University, in a single teaching hospital center between 1995 and 2014. Nephrosclerosis was diagnosed in accordance with the criteria outlined in the World Health Organization (WHO) monograph of renal diseases. All patients were followed by means of registries for 10 years to record subsequent events, if any., Outcomes: The primary study outcome was correlating the occurrence of CVD, defined as a composite of cardiovascular deaths, nonfatal and fatal myocardial infarction, and stroke, with the development of ESRD or death., Results: The mean age of patients at the time of biopsy was 54.8 ± 12.7 years (range 33-72 years). Of these patients, seven were affected by nonfatal CVD and two died due to CVD. Only one patient developed ESRD during the follow-up period. Using Kaplan-Meier analysis, risk factors for the primary study outcome were estimated to include an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2), systolic blood pressure > 130 mmHg and proteinuria > 1 g/g creatinine. Univariate analysis was used for the assessment of the relative risk for the primary study endpoint of several covariates: age, systolic blood pressure, eGFR and proteinuria at time of renal biopsy. eGFR was found to be the strongest factor determining an event-free period [relative risk (RR) =1.931, p = 0.014]., Conclusions: Patients with nephrosclerosis are at high risk of CVD when they have moderately advanced renal impairment., (© The Author(s), 2015.)

Background and Objective: Nephrotic range proteinuria can occur in patients with biopsy proven hypertensive nephrosclerosis (HN). We analysed the differential clinical and evolution characteristics of these patients compared with other glomerular diseases., Material and Method: This is a case-control descriptive analysis obtained from the renal pathology registry of our hospital. Clinical features, treatment and evolution of these patients (cases) were compared with nephrotic patients with other glomerular diseases (controls)., Results: Five point one percent of biopsies with HN diagnosis. Case/control characteristics were: proteinuria 4.7 [3-11.4] versus 5.5 [3-28.1] g/24h/1.73m(2) (P=NS). Normal albumin compared with controls (39.5 [6.4] versus 29.4 [10] g/dL; P=.001), significant oedemas only in 10 versus 63% of controls. HN were older (58.8 [12.6] versus 45.5 [19.6] years), had longer hypertension duration before renal biopsy and more previous cardiovascular events (39 versus 16%). Mean blood pressure was higher (166/90 versus 133/75mmHg; P=.01) and had worse renal outcome., Conclusions: HN must be included in the differential diagnosis of nephrotic range proteinuria in hypertensive patients. The absence of oedema and normal serum albumin are distinctive clinical characteristics that can help in decision-making before performing a renal biopsy., (Copyright © 2013 Elsevier España, S.L.U. All rights reserved.)

Background: Chronic kidney disease (CKD) is public health concern even in Asian countries. TRK-100STP, a sustained release tablet of an orally-active prostacyclin analogue, beraprost sodium, is suggested to suppress worsening of some parameters of renal filtration function, containing in slope of 1/serum creatinine (1/SCr) vs. time in a phase II clinical trial., Methods/design: We describe the design of the phase IIb/III trial of TRK-100STP, CASSIOPEIR (CRF Asian Study with Oral PGI2 derivative for Evaluating Improvement of Renal function) conducted in approximately 160 centers in China, Hong Kong, Japan, Malaysia, Republic of Korea, Taiwan, and Thailand. A total of 750 patients (n = 250 per group) with primary glomerular disease or nephrosclerosis were planned to be enrolled. Patients were randomized into one of three treatment groups in a double-bind, placebo-controlled manner: TRK-100STP 60 μg b.i.d.; TRK-100STP 120 μg b.i.d.; or placebo. The treatment period is planned to last 2 to 4 years. The primary efficacy endpoint is the renal composite endpoint including doubling of SCr and ESRD (dialysis induction, renal transplantation, or increase in SCr to ≥ 6.0 mg/dL)., Discussion: This trial targeting CKD patients is designed to (a) demonstrate the superiority of TRK-100STP over placebo using renal composite endpoints, (b) determine the recommended clinical dose, and (c) assess the safety of TRK-100STP in this population and setting., Trial Registration: ClinicalTrials.gov Identifier: NCT01090037.

Purpose: To investigate the relationship between renal function and total renal volume-vascular indices using 3D power Doppler ultrasound (3DPDUS)., Materials and Methods: One hundred six patients with hypertensive proteinuric nephropathy (HPN) (49 male, 57 female) and 65 healthy controls (32 male, 33 female) were evaluated prospectively using 3DPDUS. Total renal volume (RV), vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were calculated using Virtual Organ Computer-aided Analysis (VOCAL). The estimated glomerular filtration rates (GFRs) of the patients with HPN and the control group were calculated. The patients with HPN were divided into two groups on the basis of GFR, normal (≥90) or reduced (<90). Differences between groups were compared using ANOVA. Correlations between GFR, renal volume and vascular indices were analyzed using Pearson's correlation analysis. Significance was set at p<0.05., Results: The mean total RV, VI, FI and VFI values in the reduced GFR, normal GFR and control groups were RV (ml): 234.7, 280.7 and 294.6; VI: 17.6, 27.6 and 46.8; FI: 79.1, 88.7 and 93.9 and VFI: 7.1, 12.7 and 23.8. There were statistically significant differences between the groups (p<0.001). Total RVs and vascular indices exhibited significant correlations with estimated GFR (r=0.53-0.59, p<0.001) CONCLUSION: Three-dimensional power Doppler ultrasound is a reliable predictive technique in renal function analysis., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: Tubulointerstitial fibrosis is one of the strongest independent predictive factors in determining the prognosis in IgA nephritis. Recently, software-based quantitative measurement of interstitial fibrosis with Sirius Red staining has entered the practice. The objective of this study was to investigate the prognostic value of measurement of interstitial nephritis with this method in IgA nephritis., Method: Forty-three patients diagnosed with IgA nephritis with renal biopsy between the years 2005 and 2009 were included in this retrospective observational study. The diagnostic biopsies of 37 patients were examined. Basal data included age, gender, creatinine level, glomerular filtration rate (GFR), presence of proteinuria, hypertension, glomerulosclerosis, mesangial proliferation, and interstitial fibrosis and fibrosis index calculated by the measurement of computed images of Sirius Red positive areas. Final visit included evaluation of development of end-stage renal disease (ESRD), and GFR (whether = 60 mL/min or <60 mL/min)., Results: Numbers of patients with hypertension (75% vs. 34.5%; p = 0.050), ESRD development (62.5% vs. 20.7%, p = 0.035), GFR <60 mL/min (87.5% vs. 31%; p = 0.007) were greater; and basal GFR (34.25 ± 25.29 vs. 64.14 ± 35.34; p = 0.048) was lower in high-intensity interstitial fibrosis group (>1000 μm2) compared to low-intensity interstitial fibrosis group (≤1000 μm(2))., Conclusion: Quantitative analysis of computed imaging of areas of Sirius Red positive tubulointerstitial fibrosis might serve as an effective novel method to determine the prognosis in IgA nephritis.

A 56-year-old Japanese man developed a cerebral hemorrhage and was diagnosed with plasma cell-type multicentric Castleman's disease (MCD) based on the findings of an inguinal lymph node biopsy in addition to clinical findings, including hypergammaglobulinemia, anemia and elevation of the levels of CRP and serum IL-6. Although a renal biopsy showed nephrosclerosis, the levels of serum lipids and apolipoprotein were low. Following the initiation of treatment with anti-interleukin-6 receptor antibodies, the hypergammaglobulinemia, anemia, CRP level and serum lipid profile improved. However, inflammation due to overproduction of IL-6 persisted, and atherosclerotic vascular events occurred as critical complications, even though the serum levels of lipids were very low.

Acute kidney injury (AKI) is a well-recognized complication of minimal change nephrotic syndrome (MCNS). Previous reports support the concept that AKI associated with MCNS is reversible; however, information regarding the hemodynamic basis of AKI in MCNS is insufficient. We herein describe a case of AKI in a man with MCNS. In this case, monitoring the longitudinal changes in renal perfusion using serial Tc-99m-MAG3 renal scanning was beneficial for evaluating the pathophysiological background associated with the development of AKI. The potential impact of serial renal scanning in MCNS patients with AKI will also be discussed.

History and Admission Findings: A 38-year-old woman presented with strong headache, abdominal and chest pain. Blood pressure was 240/115 mmHg. In the emergency room lab troponin T was elevated. Further tests showed signs of hemolysis and thrombopenia. In addition kidney failure was present., Investigations: The ECG showed tachycardia, but no other changes. Echocardiography revealed hypertrophy of the left ventricle. In the eye exam hypertensive retinopathy was demonstrated. Kidney biopsy showed signs compatible with malignant hypertension., Treatment and Course: Due to chest pain and elevation of troponin T acute coronary syndrome was diagnosed. In combination with thrombopenia and hemolysis a thrombotic microangiopathy was suspected. Because of the hypertensive emergency malignant hypertension became a possible differential diagnosis. Unfortunately antiplatelet treatment precluded kidney biopsy right at the beginning. Thus, plasmapheresis was initiated together with antihypertensive treatment. Kidney biopsy was done after plasma exchange and confirmed the diagnosis of malignant hypertension., Conclusion: Diagnosis of malignant hypertension can be difficult because symptoms of thrombotic microangiopathy are frequently present. In many cases only the combination of history, exams of endorgan damage and clinical course is needed to confirm the diagnosis. Prompt and sustained lowering of the blood pressure is pivotal. Even after successful treatment patients keep an elevated cardiovascular risk and need a close follow up., (© Georg Thieme Verlag KG Stuttgart · New York.)

Hypertensive nephrosclerosis is a much overused clinical diagnosis, largely unsubstantiated by biopsy data. It is in fact a clinical-pathological diagnosis implying a causal role of hypertension in the associated chronic kidney disease. However, such a simple, linear causality is often not obvious or easy to demonstrate. Further factors like age, Afro-American descent, genetic and immunological factors as well as dysmetabolic syndrome may contribute to the development and progression of arterionephrosclerosis independently of hypertension.

Comparison of results of standard complex of survey with changes of urine levels of biological inflammatory marker (MCP-1), marker of fibrogenesis (TGF-beta1), marker of angiogenesis (VEGF), markers of nephron damage (collagen IV, alpha-GST, pi-GST) in 140 children with vesicoureteral reflux before and 6 months after treatment was performed. It was found that nephrosclerotic process occurs even at low degrees of vesicoureteral reflux. Even in the absence of structural and functional disorders of the kidneys according to traditional methods of evaluation, there were significant changes in the levels of biological markers of inflammation, fibrosis, and angiogenesis, as well as damage of main elements of the nephron. The method for calculating the "index of early renal damage" is proposed; method allows to monitor the state of the renal parenchyma of children with this disease.

Hypertensive nephropathy represents the most prevalent cause of end-stage renal disease in France. Renal lesions are unspecific. Nephroangiosclerosis diagnosis is overestimated due to non standardized clinical criteria and available histological analysis. Other factors than hypertension contribute to vascular lesions.MYH9 and APOL1 polymorphisms are strongly associated with kidney diseases including hypertensive nephropathy. Elevated blood pressure levels are associated with CKD progression. Treatment includes angiotensin blockers which have a synergic effect on blood pressure reduction and lowering urinary protein excretion with sodium restriction and diuretics., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Hypertensive nephrosclerosis is the leading cause of end stage renal disease (ESRD) in France, however, in prospective clinical trials of hypertension, ESRD accounts only for a small fraction of all events (incidence rate 0.2 to 0.4% by year). Hypertensive nephrosclerosis is characterized histologically by a series of vascular injury, none of which is truly specific and that can be observed also in obesity or normal aging. Hypertensive nephrosclerosis is mildly symptomatic, but the prognosis is never benign, due to cardiovascular and renal burden. This unspecific presentation may explain why the diagnosis of hypertensive nephrosclerosis is easily carried by excess, the main differential diagnoses are atherosclerotic ischemic renal disease, poorly symptomatic primitive nephropathies or the sequelae of unnoticed malignant hypertensive nephrosclerosis. The very high prevalence of hypertensive nephrosclerosis in populations from African ancestry has suggested a genetic predisposition. MYH9/APOL1 gene variants have recently been identified and are strongly associated with hypertensive nephrosclerosis, however the pathophysiological link between these variants and renal disease is still unclear. The treatment is mainly based on blocking the renin angiotensin system, especially when proteinuria is present. The target blood pressure is less firmly established, the latest data from the AASK study, however, do suggest a benefit on progression of lower values < 135/80 or even < 130/80 mmHg, especially in patients with proteinuria., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Objective: We investigated the present state of, and trends in, hemodialysis therapy in Wakayama, with the aim of identifying present and future problems., Methods: We compared the number of patients on maintenance hemodialysis, patients newly commencing hemodialysis each year, and proportion of diseases prompting the initiation of hemodialysis, between Wakayama and all Japan from 2002 to 2009, using the CD-ROM, "An overview of dialysis treatment in Japan," published by the Japanese Society for Dialysis Therapy., Results: The number of patients on maintenance hemodialysis per head of population was higher in Wakayama than in all Japan throughout the study period. The number of patients newly commencing hemodialysis per head of population was higher in Wakayama than in all Japan from 2002 to 2004, but no significant difference was seen after 2005. The proportion of patients with chronic glomerulonephritis as the causative disease for hemodialysis initiation was higher in Wakayama than in all Japan. However, nephrosclerosis was less common as the causative condition in Wakayama than in all Japan. The proportions of the different causative diseases were similar in all patients on maintenance hemodialysis in Wakayama as in the newly initiated patients. Accordingly, some patients diagnosed with chronic glomerulonephritis might actually have nephrosclerosis, or treatment may be inadequate., Conclusion: In order to reduce the number of patients requiring maintenance hemodailysis, it is important to accurately differentiate between chronic glomerulonephritis and nephrosclerosis, and also to treat patients with either disease appropriately.

Background: Hypertensive nephrosclerosis alone and in combination with other renal diseases is a leading cause of terminal renal insufficiency. Histologic lesions manifest as benign nephrosclerosis (bN) with arteriolar hyalinosis and later fibrosis. Procoagulant micromilieus have been implicated in fibrosis. Hyalinosis is considered to consist of plasma insudation possibly containing procoagulant factors like von Willebrand factor (VWF). Therefore, it is hypothesized that VWF cleaving protease ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type-1 motif, 13) is normally expressed by arteriolar vascular smooth muscle cells (VSMCs) and diminished in bN and that this reduction contributes to fibrosis in bN., Methods: ADAMTS13 expression was examined by immunohistochemistry and quantitative real-time polymerase chain reaction in VSMCs of various human organs. Fifty-four specimens with and seven without bN were immunostained for ADAMTS13, VWF, CD61 and VSMC differentiation markers in arteriolar walls., Results: Expression of ADAMTS13 is confirmed in VSMCs. In bN, ADAMTS13 immunostaining of arterial VSMCs correlated inversely with fibrotic but not hyalinotic lesions. Smooth muscle myosin heavy chain showed an inverse correlation with hyalinotic, as opposed to fibrotic lesions of bN. Smoothelin showed an inverse correlation with both hyalinotic and fibrotic lesions of bN. VWF was absent in normal controls and hyalinotic lesions, but present exclusively in fibrotic lesions in 7/54 (13%) bN cases. CD61 was absent in all arteriolar walls., Conclusions: The present results establish ADAMTS13 as a novel marker of contractile VSMCs that is retained in early hyalinotic bN but partially lost later in fibrotic bN. Loss of ADAMTS13 and accumulation of VWF in fibrotic but not hyalinotic arteriolar walls could further propagate fibrosis in bN.

Renal mechanisms, in particular the renin-angiotensin system and renal salt handling, are of major importance in blood pressure regulation. Co-existence of hypertension and decreased renal function may be due to nephrosclerosis secondary to hypertension, or primary renal disease with secondary hypertension. Mild degrees of chronic kidney disease (CKD) can be detected in around 10% of the population, and detection is important as CKD is an important risk factor for atherosclerotic cardiovascular disease. Conversely, heart failure may cause an impairment of renal function. In chronic progressive nephropathy, effective blood pressure lowering is of paramount importance, and angiotensin converting enzyme inhibitors and angiotensin receptor blockers are agents of choice.

The morphological findings of so-called hypertensive nephrosclerosis, rather than implying a linear direct relationship to damage induced by hypertension, may indicate complex environmental and genetic factors, which together foster the coexistence of renal lesion and hypertension in this clinical setting. We discuss the clinical and pathological criteria for diagnosis of arterionephrosclerosis, and possible pathogenetic factors, including hypertension, ethnicity, aberrant autoregulation, prothrombotic mechanisms, low birth weight, decreased nephron number, genetic factors and dysmetabolic syndrome.

Objective: To investigate the clinical and pathological characteristics of patients with clinically presumed hypertensive nephrosclerosis (HN)., Methods: Clinical data and renal biopsy results were obtained in 63 patients diagnosed clinically as HN (primary hypertension plus renal injury)., Results: HN was confirmed by biopsy in 47 out of 63 patients (74.6%, 12 malignant nephrosclerosis and 35 benign nephrosclerosis). Primary nephritis (PN) was diagnosed by biopsy in 10 patients (7 IgA nephropathy, 2 mesangial proliferative nephritis, 1 chronic interstitial nephritis) and focal and segmental glomerulosclerosis (FSGS) in 6 patients. Blood pressure, body mass index, GFR and blood lipids were similar among groups. HN patients were related to higher age, more frequent family history of hypertension, longer hypertension duration, higher left ventricular mass index, lower serum creatinine and lower incidence of microscopic hematuria. Most patients with malignant nephrosclerosis and FSGS patients showed grades III and IV retinopathy., Conclusion: Our results show that HN was misdiagnosed in nearly 25% patients in this cohort. Since the clinical features are similar between HN, PN and FSGS, renal biopsy is needed to establish the diagnosis of HN.

Cholesterol crystal embolization (CCE) is a dreaded complication of radiology, vascular surgery, and/or anticoagulation in patients with atherosclerosis and ulcerated aortic plaques. It also represents a cause of early graft failure and of poor results of renal artery surgery. Crystals lodge in small caliber renal arteries, where they induce early, transitory thrombosis followed by delayed, definitive obstruction by endarteritis, accompanied by evidence of inflammation and eosinophilia. Massive CCE leads to early oligoanuria. In subacute forms, renal insufficiency is often delayed by weeks or months following the triggering event. A third, chronic subset of CCE is easily mistaken for atherosclerotic renal ischemia and/or nephrosclerosis. The kidney is rarely the sole organ involved in acute/subacute forms, in which the central nervous system, the coronary arteries, the spinal cord, and the mesenteric and pancreatic blood supply compromise represent the main causes of death. Cutaneous, retinal, and muscle involvement allow diagnosis by inspection or scarcely invasive biopsies in about 80% of cases, whereas renal biopsy as the only diagnostic procedure is required in 20% of cases. Prevention is based on avoidance of endovascular radiology maneuvers, vascular surgery, and excess anticoagulation in atherosclerotic patients. Treatment of acute/subacute forms of renal insufficiency consisting of stopping anticoagulation and forbidding any new radiologic and/or vascular surgery procedure; treating hypertension with angiotensin 2 antagonists and vasodilators, strict volemic control by loop diuretics and ultrafiltration, along with parenteral nutrition and prednisone, has been credited with improved outcome. Iloprost may obtain favorable results. Statins definitely ameliorate the renal and patient's prognosis.

Objective: The diagnosis of renal failure with a normal urinalysis represents a short differential diagnosis that has not been characterized in the literature. This study was designed to identify the specific disease states that encompass this interesting renal condition., Material: The Regenstrief database, which is an electronic medical record containing inpatient laboratory and other clinical data for patients admitted to Wishard Memorial Hospital, was utilized to provide data for this study., Methods: The database was culled to provide data for hospitalized patients admitted between March 1, 1992, and March 1, 2001, with the concurrent findings of a serum creatinine greater than or equal to 2 mg/dL, a normal urinalysis, and diagnoses of obstructive uropathy, multiple myeloma, prerenal azotemia, hypertensive nephrosclerosis, interstitial nephritis, renal vascular disease, hypokalemic nephropathy, and hypercalcemia, as identified by their corresponding ICD-9 codes., Results: A search of the Regenstrief database yielded a total of 190,343 patient admissions. There were 515 patient admissions with renal failure and a concurrent normal urinalysis. The largest specific diagnostic categories within this group were hypertension and prerenal azotemia., Conclusions: An elevated serum creatinine and normal urinalysis present a short differential for the etiologies of renal failure and include such entities as hypertensive nephrosclerosis, prerenal azotemia, obstructive nephropathy, interstitial nephritis, renal vascular disease, and various electrolyte abnormalities. An awareness of these specific disease states may lead to an earlier diagnosis and more effective treatment of renal failure.

Background: Scarring is known to be the endpoint of most chronic kidney diseases. Therefore, prevention of renal fibrosis is a very important topic. The hereditary type IV collagen disease Alport's syndrome is a rare, but challenging cause of chronic renal fibrosis., Pathogenesis of Glomerular and Interstitial Renal Fibrosis in Humans: Increasing knowledge about the pathogenesis of Alport's syndrome may help to find principles of nephro-protection in chronic renal diseases. The defect gene in Alport's syndrome causes an altered assembly of extracellular matrix leading to a defect cell-matrix interaction and fibrosis. This scarring is regulated by comparable mechanisms as in diabetic nephropathy or chronic inflammatory renal diseases. NEPHRO-PROTECTION IN ANIMAL MODELS: By using an Alport animal model of chronic renal fibrosis, principles of nephro-protective therapies such as blockade of the renin-angiotensin system or the effect of HMG-CoA reductase inhibitors can be investigated. CURRENT AND FUTURE NEPHRO-PROTECTION IN HUMANS: The same model serves for evaluation of new organo-protective therapies such as vasopeptidase inhibitors, blockade of endothelin, chemokine and collagen receptors as well as stem cell therapy and their potential benefit for patients with chronic renal diseases.

The link between the kidney and hypertension has been considered a villain-victim relationship. High blood pressure levels are a well-recognized feature in chronic renal disease, but the ability of mild-to-moderate hypertension to produce renal insufficiency has been questioned. Nephrosclerosis, benign nephrosclerosis, and hypertensive kidney disease are terms that clinicians use when renal damage is thought to be secondary to essential hypertension. Many cases of end-stage renal disease are ascribed to so-called benign nephrosclerosis. This entity could actually be a primary renal disease affecting the preglomerular microvasculature, perhaps genetically mediated and ethnically influenced, and showing a heterogeneous clinical expression. African Americans suffer from nephrosclerosis more frequently than Caucasians. Nephrosclerosis affecting Caucasians seems to show a less aggressive pattern and could represent early age-related renal sclerosis. The risk of end-stage renal disease is increased when atherosclerotic lesions in large renal arteries coexist. Age, systolic blood pressure, proteinuria, and concomitant cardiovascular disease are well-known promoters of renal failure. A multifactorial strategy, including antihypertensive and antiproteinuric drugs, and lipid-lowering and anti-platelet agents, could improve cardiovascular and renal outcomes in patients with nephrosclerosis.

Four apolipoprotein (apo) E variants have been reported to be associated with lipoprotein glomerulopathy (LPG), which is characterized by type III hyperlipoproteinemia (type III HLP) and proteinuria and frequently leads to nephrotic syndrome. We report the histologic findings in the kidneys of a type III HLP patient with an apo E variant, apo E Toranomon, in which the glutamine at residue 187 in apo E is substituted by glutamic acid (Q187E). The patient also had type 2 diabetes mellitus. No evidence of lipoprotein thrombi suggestive of LPG was detected, however, and the histologic diagnosis was diabetic nephrosclerosis. This unique case illustrates that not all apo E variants result in LPG, and the location of mutations in the apo E protein is one of the important determinants for the development of LPG., (Copyright 2002 by the National Kidney Foundation, Inc.)

Essential hypertension causes renal injury. Hypertensive nephroangiosclerosis (HN) or hypertensive nephropathy are terms most commonly used to describe this renal pathology. Although specific histological lesions occurring in affected kidneys are well known, pathogenesis of hypertension-related renal scarring is not completely understood. Evidence exists to support the theory that other factors such as aging, black race or smoking, beside blood pressure, contribute to the development and progression of HN. Metabolic disturbances, cocaine and nonsteroidal anti-inflammatory drug abuse, ochratoxin A exposure, dietary salt intake, heavy metal toxicity, hantavirus infection and perinatal programming are also considered risk factors. Renal susceptibility genes may determine whether hypertension-induced progressive renal damage occurs and how severe it is. Determination of all risk factors may identify patients at high risk of renal failure and help tailor an appropriate management. In the present paper, the knowledge available on this clinically important objective is discussed., (Copyright 2002 S. Karger AG, Basel)

Nephroangiosclerosis and nephrosclerosis are terms used to define the renal disease induced by essential hypertension. The predominant histologic changes occur in the preglomerular microvasculature. Epidemiological data about the risk of hypertensive patients from developing renal failure offer conflicting results. Nevertheless, renal vascular disease, including nephroangiosclerosis and/or ischemic nephropathy, appears to be an important cause of end-stage renal disease. Presumably, nephrosclerosis is the renal expression of systemic atherosclerosis: male sex, age > 55-60 years, black race, high serum cholesterol and/or uric acid levels, and coronary heart disease, peripheral artery disease, and/or cerebrovascular disease are common associations with the renal alteration. Treatment strategy should include an intensive blood pressure control, probably below 130/80 mmHg, together with antiplatelet and lipid-lowering agents when necessary. Although specific studies are lacking, ACE inhibitors and angiotensin II antagonists may offer additional benefits in slowing the renal disease progression.

It is currently unclear whether hypertensive nephrosclerosis (HN), usually diagnosed solely on clinical grounds, is a relevant cause of end-stage renal disease. We biopsied 81 hypertensive outpatients (blood pressure >/=160/95 mm Hg) with moderate renal insufficiency, who were referred to our service from 1988 to 1998. Patients with known causes of hypertension, systemic disorders, rheumatic disease, or nephrotic syndrome were excluded. In 65% of patients, HN was the sole histological abnormality associated with renal dysfunction. Benign nephrosclerosis (BN), defined as isolated arteriolar hyalinosis and/or intimal fibrosis, was found in 18 HN patients (22%), whereas malignant nephrosclerosis (MN), denoted mainly by myointimal cell proliferation, appeared in 35 HN patients (43%). Previously undiagnosed primary nephritis (PN) was found in 13 patients (16%), whereas focal and segmental glomerulosclerosis, which might be either primary or secondary to hypertension, appeared in 15 patients (19%). These findings suggest that HN, in both its BN and MN forms, can be a definite cause of chronic renal insufficiency and that a substantial fraction of patients with renal insufficiency and clinical diagnosis of HN may actually have PN.