Transcriptomic analysis reveals partial epithelial-mesenchymal transition and inflammation as common pathogenic mechanisms in hypertensive nephrosclerosis and Type 2 diabetic nephropathy.

Hypertensive nephrosclerosis (HN) and Type 2 diabetic nephropathy (T2DN) are the leading causes of chronic kidney disease (CKD). To explore shared pathogenetic mechanisms, we analyzed transcriptomes of kidney biopsies from patients with HN or T2DN. Total RNA was extracted from 10 µm whole kidney sections from patients with HN, T2DN, and normal controls (Ctrl) (n = 6 for each group) and processed for RNA sequencing. Differentially expressed (log2 fold change >1, adjusted p < 0.05) genes (DEG) and molecular pathways were analyzed, and selected results were validated by immunohistochemistry (IHC). ELISA on serum samples was performed on a related cohort consisting of patients with biopsy-proven HN (n = 13) and DN (n = 9), and a normal control group (n = 14). Cluster analysis on RNA sequencing data separated diseased and normal tissues. RNA sequencing revealed that 88% (341 out of 384) of DEG in HN were also altered in T2DN, while gene set enrichment analysis (GSEA) showed that over 90% of affected molecular pathways, including those related to inflammation, immune response, and cell-cycle regulation, were similarly impacted in both HN and T2DN samples. The increased expression of genes tied to interleukin signaling and lymphocyte activation was more pronounced in HN, while genes associated with extracellular matrix organization were more evident in T2DN. Both HN and T2DN tissues exhibited significant upregulation of genes connected with inflammatory responses, T-cell activity, and partial epithelial to mesenchymal transition (p-EMT). Immunohistochemistry (IHC) further confirmed T-cell (CD4+ and CD8+ ) infiltration in the diseased tissues. Additionally, IHC revealed heightened AXL protein expression, a key regulator of inflammation and p-EMT, in both HN and T2DN, while serum analysis indicated elevated soluble AXL levels in patients with both conditions. These findings underline the shared molecular mechanisms between HN and T2DN, hinting at the potential for common therapeutic strategies targeting both diseases.

Trends in the incidence of renal replacement therapy by type of primary kidney disease in Japan, 2006-2020.

AIM: Age-standardized incidence of end stage kidney disease requiring renal replacement therapy (RRT) has stabilized in men and declined in women in Japan since 1996. However, recent trends by primary kidney disease are unknown. The present study aimed to examine recent trends in incidence rates of RRT by primary kidney disease in Japan. METHODS: Numbers of incident RRT patients aged ≥20 years by sex and primary kidney disease from 2006 to 2020 were extracted from the Japanese Society of Dialysis Therapy registry. Using the census population as the denominator, annual incidence rates of RRT were calculated and standardized to the WHO World Standard Population (2000-2025). Average annual percentage change (AAPC) and corresponding 95% confidence intervals (CIs) were calculated for trends using Joinpoint regression analysis. RESULTS: From 2006 to 2020, the crude number of incident RRT patients due to nephrosclerosis increased by 132% for men and 62% for women. Age-standardized incidence rates of RRT due to nephrosclerosis increased significantly, by 3.3% (95% CI: 2.9-3.7) and 1.4% (95% CI: 0.8-1.9) per year for men and women, respectively. The AAPC of chronic glomerulonephritis (-4.4% [95% CI: -5.3 to -3.8] for men and -5.1% [95% CI: -5.5 to -4.6] for women) and diabetic nephropathy (-0.6% [95% CI: -0.9 to -0.3] for men and -2.8% [95% CI: -3.1 to -2.6] for women) significantly decreased from 2006 to 2020. CONCLUSION: Incident RRT due to chronic glomerulonephritis and diabetic nephropathy decreased, while the number and incident rates of RRT due to nephrosclerosis increased, from 2006 to 2020 in Japan.

Nephrosclerosis in young patients with malignant hypertension.

BACKGROUND: Nephrosclerosis is one of the histopathological consequences of severe or malignant hypertension (MH), some of the pathophysiology of which has been extrapolated from essential polygenetic arterial hypertension. Despite our recent description of unsuspected ciliopathies with MH, causes of MH in young patients with severe renal impairment are poorly understood. METHODS: To refine and better describe the MH phenotype, we studied clinical and prognostic factors in young patients receiving a kidney biopsy following their first episode of MH. Patients were identified retrospectively and prospectively from eight centres over a 35-year period (1985-2020). Keywords were used to retrospectively enrol patients irrespective of lesions found on renal biopsy. RESULTS: A total of 114 patients were included, 77 (67%) of whom were men, average age 34 years, 35% Caucasian and 34% African origin. An isolated clinical diagnosis of severe nephrosclerosis was suggested in only 52% of cases, with 24% primary glomerulopathies. Only 7% of patients had normal renal function at diagnosis, 25% required emergency dialysis and 21% were eventually transplanted. Mortality was 1% at the last follow-up. Independent prognostic factors significantly associated with renal prognosis (6-month dialysis) and predictive of end-stage renal disease were serum creatinine on admission {odds ratio [OR] 1.56 [95% confidence interval (CI) 1.34-1.96], P < .001} and renal fibrosis >30% [OR 10.70 (95% CI 1.53-112.03), P = .03]. Astonishingly, the presence of any thrombotic microangiopathy lesion on renal biopsy was an independent, protective factor [OR 0.14 (95% CI 0.02-0.60), P = .01]. The histopathological hallmark of nephrosclerosis was found alone in only 52% of study patients, regardless of ethnicity. CONCLUSIONS: This suggests that kidney biopsy might be beneficial in young patients with MH.

Mesangial Injury and Capillary Ballooning Precede Podocyte Damage in Nephrosclerosis.

The development of focal and segmental glomerulosclerosis (FSGS) as a consequence of glomerular hypertension resulting from arterial hypertension is widely considered a podocyte disease. However, the primary damage is encountered in the mesangium. In acute settings, mesangial cells disconnect from their insertions to the glomerular basement membrane, causing a ballooning of capillaries and severe changes of the folding pattern of the glomerular basement membrane, of the arrangement of the capillaries, and thereby of the architecture of the tuft. The displacement of capillaries led to contact of podocytes and parietal epithelial cells, initiating the formation of tuft adhesions to Bowman's capsule, the committed lesion to progress to FSGS. In addition, the displacement of capillaries also caused an abnormal stretching of podocytes, resulting in podocyte damage. Thus, the podocyte damage that starts the sequence to FSGS is predicted to develop secondary to the mesangial damage. This sequence was found in two hypertensive rat models of FSGS and in human hypertensive nephrosclerosis.

Autopsy study examining non-chronic kidney disease versus chronic kidney disease caused by hypertensive-nephrosclerosis in elderly subjects.

BACKGROUND: The aim of this autopsy study was to clarify the differences of renal histopathology between non-chronic kidney disease (CKD) and CKD caused by hypertensive-nephrosclerosis in the elderly and during the aging process. METHODS: We examined autopsy specimens from 105 elderly patients (53 male subjects; mean age, 86.2 years) including 44 patients with CKD as a result of nephrosclerosis. The analysis was divided into two groups depending on whether they had CKD. RESULTS: The incidences of arterial intimal thickening (AIT), obsolescent-type global glomerulosclerosis (OB), and interstitial fibrosis and tubular atrophy (IF/TA) were higher in the CKD group than in the non-CKD group (all p < 0.01). These factors were all correlated with each other (AIT vs. OB, r = 0.43; AIT vs. IF/TA, r = 0.25; OB vs. IF/TA, r = 0.53). IF/TA had the strongest association with hypertension and decreased eGFR. In the non-CKD group, the frequency of OB was more than 20% in subjects aged 90 years or older. However, the individuals in the non-CKD group tended to have compensatory glomerular hypertrophy with increasing age and a retained eGFR, while the CKD group was unable to obtain compensatory hypertrophy and had a lower eGFR. We also found that AIT, OB and IF/TA occurred independently of systemic atherosclerosis. CONCLUSIONS: Non-CKD in the elderly refers to the so-called aging kidney. The progression from aging kidney to CKD caused by nephrosclerosis was influenced by increases in AIT, OB and IF/TA. IF/TA was thought to be the most important downstream factor in the progression of aging kidney to CKD.

Vascular, cardiac, and renal lesions attributed to primary systemic hypertension in western pygmy marmosets (Cebuella pygmaea).

In a retrospective study of a western pygmy marmoset (Cebuella pygmaea) colony, postmortem examination of 1/8 juvenile and 29/47 adult animals identified vascular, cardiac, and renal lesions consistent with systemic hypertension. This included frequent renal arteriolar hypertrophy, hyaline and proliferative arteriolosclerosis, fibrinoid necrosis of arterioles, glomerulosclerosis, and nephrosclerosis. Affected animals ranged from 0.6 to 12 years of age (mean 6 years) and had an observed male predominance. Genealogical relatedness was evident in several breeding pairs and spanned multiple generations. Concurrent cardiac and renal disease was commonly identified, although frequently subclinical, and both were important causes of morbidity and mortality in affected animals. Cardiomegaly and hypertrophy were typical features and were accompanied by left atrial thrombosis in 10 animals. Signs of heart failure included chronic pulmonary edema in 20 cases and body cavity effusions in 17. In the kidneys, 19 cases had glomerular disease and hypertensive vasculopathy, and 26 cases had nephrosclerosis or glomerulosclerosis. Common extrarenal secondary causes of hypertension were excluded by necropsy examination. The pathogenesis is suggested to involve primary hypertension leading to renal and cardiac disease. Elevated sympathetic activity might be an underlying factor in the frequent development of primary systemic hypertension in the pygmy marmoset, as for the owl monkey.

Nephrosclerosis impacts time trajectory of renal function and outcomes in elderly individuals with chronic kidney disease.

Despite hypertension ranks among the leading causes of chronic kidney disease (CKD), the impact of chronic hypertensive nephropathy, the so-called 'nephrosclerosis' (NS), on CKD progression is often unpredictable, particularly in elderly population. We have conducted a prospective, observational study to define renal function patterns and outcomes in elderly CKD individuals with or without NS. Three hundred four individuals with an already established CKD were categorized according to the etiology of CKD. NS was defined as the presence of CKD associated with long-term essential hypertension, hypertensive retinopathy, left ventricular hypertrophy and minimal proteinuria. Time trajectories in estimated glomerular filtration rate (eGFR) (CKD-Epi) were computed over a 4-year follow-up. In addition, we analyzed the occurrence of a composite outcome of doubling of serum creatinine levels, eGFR reduction ≥25% and/or the need of chronic renal replacement therapy. CKD was secondary to nephrosclerosis (CKD-NS) in 220 (72.3%). In the whole cohort, the average estimated annual GFR slope was 1.8 mL/min/1.73 m2 eGFR decline was slower in CKD-NS as compared with others (1.4 vs 3.4 mL/min/1.73 m2; p<0.001). The composite renal outcome during follow-up occurred less frequently among elderly with CKD-NS (16/204 vs 14/70; p=0.01, crude HR 0.43, 95% CI 0.22 to 0.85) and was associated at logistic analyses with the etiology of CKD, background cardiovascular disease, total and low density lipoproteins (LDL) cholesterol, and glycemia levels (p value was ranging from 0.01 to 0.05). Despite being highly prevalent in the elderly, NS is associated with a more favorable renal disease course as compared with other conditions.

Idiopathic hypereosinophilic syndrome in hemodialysis patients: Case reports.

RATIONALE: Herein, we report 3 hemodialysis patients with idiopathic hypereosinophilic syndrome who were successfully treated using corticosteroid therapy. PATIENT CONCERNS: Case 1 was a 63-year-old man who was undergoing hemodialysis because of bilateral nephrectomy and developed hypereosinophilia with digestive symptoms, myocardial injury, and intradialytic hypotension. Case 2 was an 83-year-old man who was undergoing hemodialysis because of nephrosclerosis and developed hypereosinophilia with pruritus, myocardial injury, and intradialytic hypotension. Case 3 was a 59-year-old man who was undergoing hemodialysis because of diabetic nephropathy and developed hypereosinophilia with pruritus, myocardial injury, and intradialytic hypotension. DIAGNOSES: All 3 patients presented with hypereosinophilia (eosinophil count ≥1500 /µL for more than 1 month) and multiple-organ involvement (intradialytic hypotension, cardiac injury, digestive symptoms, and allergic dermatitis). A specific cause for the hypereosinophilia was not identified by systemic computed tomography, electrocardiography, echocardiography, bone marrow examination, or blood tests. Furthermore, Case 2 and 3 had not recently started taking any new drugs and drug-induced lymphocyte stimulation tests were negative in Case 1. Therefore, they were diagnosed with idiopathic hypereosinophilic syndrome. INTERVENTIONS: All 3 patients received corticosteroid therapy with prednisolone at a dose of 40 mg/d, 30 mg/d, and 60 mg/d in Case 1, 2, and 3, respectively. OUTCOMES: Their digestive symptoms, pruritus, intradialytic hypotension, and serum troponin I concentrations were immediately improved alongside reductions in their eosinophil counts. LESSONS: There have been few case reports of idiopathic hypereosinophilic syndrome in patients undergoing hemodialysis. We believe that recording of the clinical findings and treatments of such patients is mandatory to establish the optimal management of idiopathic hypereosinophilic syndrome.

Hypertensive nephrosclerosis: wider kidney biopsy indications may be needed to improve diagnostics.

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.

Performance of the Kidney Failure Risk Equation by Disease Etiology in Advanced CKD.

BACKGROUND AND OBJECTIVES: The kidney failure risk equation is a clinical tool commonly used for prediction of progression from CKD to kidney failure. The kidney failure risk equation's accuracy in advanced CKD and whether this varies by CKD etiology remains unknown. This study examined the kidney failure risk equation's discrimination and calibration at 2 and 5 years among a large tertiary care population with advanced CKD from heterogeneous etiologies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included 1293 patients with advanced CKD (median eGFR 15 ml/min per 1.73 m2) referred to the Ottawa Hospital Multi-Care Kidney Clinic between 2010 and 2016, with follow-up clinical data available through 2018. Four-variable kidney failure risk equation scores for 2- and 5-year risks of progression to kidney failure (defined as dialysis or kidney transplantation) were calculated upon initial referral and correlated with the subsequent observed kidney failure incidence within these time frames. Receiver operating characteristic curves and calibration plots were used to measure the discrimination and calibration of the kidney failure risk equation both in the overall advanced CKD population and by CKD etiology: diabetic kidney disease, hypertensive nephrosclerosis, GN, polycystic kidney disease, and other. Pairwise comparisons of the receiver operating characteristic curves by CKD etiology were performed to compare kidney failure risk equation discrimination. RESULTS: The kidney failure risk equation provided adequate to excellent discrimination in identifying patients with CKD likely to progress to kidney failure at the 2- and 5-year time points both overall (2-year area under the curve, 0.83; 95% confidence interval, 0.81 to 0.85; 5-year area under the curve, 0.81; 95% confidence interval, 0.77 to 0.84) and across CKD etiologies. The kidney failure risk equation displayed adequate calibration at the 2- and 5-year time points both overall and across CKD etiologies (Hosmer-Lemeshow P≥0.05); however, the predicted risks of kidney failure were higher than the observed risks across CKD etiologies with the exception of polycystic kidney disease. CONCLUSIONS: The kidney failure risk equation provides adequate discrimination and calibration in advanced CKD and across CKD etiologies.

Amplified Association Between Blood Pressure and Albuminuria in Overweight Patients With Biopsy-Proven Hypertensive Nephrosclerosis.

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 (ß = 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.

Clinicopathological predictors for progression of chronic kidney disease in nephrosclerosis: a biopsy-based cohort study.

BACKGROUND: Biopsy-based studies on nephrosclerosis are lacking and the clinicopathological predictors for progression of chronic kidney disease (CKD) are not well established. METHODS: We retrospectively assessed 401 patients with biopsy-proven nephrosclerosis in Japan. Progression of CKD was defined as new-onset end-stage renal disease, decrease of estimated glomerular filtration rate (eGFR) by ≥50% or doubling of serum creatinine, and the sub-distribution hazard ratio (SHR) with 95% confidence interval (CI) for CKD progression was determined for various clinical and histological characteristics in competing risks analysis. The incremental value of pathological information for predicting CKD progression was assessed by calculating Harrell's C-statistics, the Akaike information criterion (AIC), net reclassification improvement and integrated discrimination improvement. RESULTS: During a median follow-up period of 5.3 years, 117 patients showed progression of CKD and 10 patients died before the defined kidney event. Multivariable sub-distribution hazards model identified serum albumin (SHR 0.48; 95% CI 0.35-0.67), hemoglobin A1c (SHR 0.71; 95% CI 0.54-0.94), eGFR (SHR 0.98; 95% CI 0.97-0.99), urinary albumin/creatinine ratio (UACR) (SHR 1.18; 95% CI 1.08-1.29), percentage of segmental/global glomerulosclerosis (%GS) (SHR 1.01; 95% CI 1.00-1.02) and interstitial fibrosis and tubular atrophy (IFTA) (SHR 1.52; 95% CI 1.20-1.92) as risk factors for CKD progression. The C-statistic of a model with only clinical variables was improved by adding %GS (0.790 versus 0.796, P < 0.01) and IFTA (0.790 versus 0.811, P < 0.01). The reclassification statistic was also improved after adding the biopsy data to the clinical data. The model including IFTA was superior, with the lowest AIC. CONCLUSIONS: The study implies that in addition to the traditional markers of eGFR and UACR, we may explore the markers of serum albumin and hemoglobin A1c, which are widely available but not routinely measured in patients with nephrosclerosis, and the biopsy data, especially the data on the severity of interstitial damage, for the better prediction of CKD progression in patients with nephrosclerosis.

Impact of high mortality in incident dialysis patients due to hypertensive nephrosclerosis: a multicenter prospective cohort study in Aichi, Japan.

INTRODUCTION: An increasing number of patients worldwide require dialysis as a result of hypertensive nephrosclerosis (HTN). However, in Japan, mortality in patients with end-stage renal disease (ESRD) has not been well by primary kidney disease including HTN and diabetic nephropathy (DN). Hence, we examined the differences in mortality among the primary kidney diseases of incident dialysis patients. METHODS: The study was a multicenter prospective cohort analysis including 1520 incident dialysis patients in Aichi prefecture, Japan. We classified patients into three groups according to the primary kidney disease [i.e., a HTN group, n = 384, a DN group n = 658, and a chronic glomerulonephritis (CGN) group, n = 224]. In addition, we classified patients into the HTN group and the DN group using propensity score matching. We compared outcomes including all-cause and infection-related mortality. RESULTS: The mortality rates of the HTN, the DN, and the CGN group, were 135.9, 64.2, and 34.8 per 1000 patient years, respectively. All-cause mortality and infection-related mortality rates in the HTN group were as high as those in the DN group after adjustment for age, gender, history of cardiovascular disease, and estimated glomerular filtration rate. No significant difference of all-cause mortality was observed after propensity score matching between the two groups (Logrank test: p = 0.523). CONCLUSIONS: The present study was Japan's first large-scale prospective cohort to demonstrate that HTN is the second most common cause of ESRD. In addition, the prognosis of patients with HTN was as poor as that of patients with DN.

First case report of using Ofatumumab in kidney transplantation AB0 incompatible. / PRIMO CASE REPORT DI UTILIZZO DELL' OFATUMUMAB NEL TRAPIANTO RENALE AB0 INCOMPATIBILE.

Modern methods for desensitization protocol rely heavily on combined apheresis therapy and Rituximab, a chimeric (murine and human) anti-CD20 antibody used in AB0 incompatible kidney transplants. Severe infusion related reactions due to the administration of Rituximab are reported in 10% of patients. These adverse reactions may hinder the completion of the desensitization protocol. Therefore, it's useful to test alternative B cell depleting therapies. Our clinical case focuses on a 41-year-old male who developed an adverse infusion reaction following the administration of Rituximab and was given Ofatumumab as an alternative treatment. Ofatumumab is a fully humanized monoclonal anti-CD20 antibody. As a fully humanized antibody, Ofatumumab may avoid immunogenic reactions. The patient tolerated the administration of the drug showing no signs of adverse side effects and with good clinical efficacy. Our case report suggest that Ofatumumab is a valid alternative B cell depleting agent.

Malignant hypertension as a rare cause of thrombotic microangiopathy.

Malignant hypertension can occasionally be associated with microangiopathic haemolytic anaemia. A 38-year-old male presented with nausea, vomiting, loss of appetite and oliguria for 2 weeks. He was diagnosed with hypertensive emergency with cardiac and renal dysfunction. Interestingly, further workup was diagnostic for the presence of thrombotic microangiopathy (TMA): haemoglobin =12.7 g/dL, indirect bilirubin =2.0 mg/dL, haptoglobin ≤6 mg/dL, platelet count =121 000/µL and schistocytes on peripheral smear. At the outset, the cause of TMA was unclear. Patient denied having diarrhoea, making haemolytic uremic syndrome less likely. A normal ADAMTS13 activity test ruled out thrombotic thrombocytopaenic purpura. Malignant hypertension induced TMA was highest on the differential and plasma exchange was deferred. Renal biopsy revealed features of TMA and malignant nephrosclerosis. Patient eventually became dialysis dependent. Aggressive blood pressure control was obtained with multiple medications.

Malignant nephrosclerosis in a patient with familial Mediterranean fever.

A 37-year-old man was admitted to our hospital for an evaluation of renal dysfunction and hypertension. The C-reactive protein level was 6.0 mg/dL, and the serum renin activity was extremely high. A renal biopsy showed malignant nephrosclerosis-like lesions with an onion skin pattern. He had a history of recurrent abdominal pain associated with periodic fevers above 38 degrees that resolved within three days. A MEditerranean FeVer (MEFV) gene analysis revealed that he was homozygous for the E148Q polymorphism (exon 2) and heterozygous for the L110P polymorphism (exon 2). The present case demonstrates that persistent subclinical inflammation can lead to malignant nephrosclerosis in familial Mediterranean fever patients with this genotype.

Dialysis-associated pseudoporphyria successfully treated with vitamin D. Report of two cases.

Pseudoporphyria refers to a rare bullous dermatosis characterized by the clinical and histological features of porfiria cutanea tarda without abnormalities in porphyrin metabolism. The pathogenesis is heterogeneous and several exogenous factors may promote the bullous lesion formation, including medications, end stage renal disease, dialysis and tanning beds. Regarding treatment of this condition, in literature different therapy have been reported, such as glutathione and his precursor N-acetylcysteine, which presents anti-oxidant properties; however even more toxic drugs, such as chloroquine, are used. Moreover, in patients with drug-induced PP discontinuation of the offending agent, if possible, is a crucial aspect of the clinical management. We report two cases of dialysis patients presenting blisters on extremities, which healed with the avoidance of UV exposure and oral Vitamin D supplementation. Interestingly Vitamin D despite the lack of antioxidant properties led to a completely resolution of PP in both our patients within 30 days. A possible explanation of this finding is that Vitamin D, playing a key role in the regulation of serum Ca2+, can modulated cadherin-cadherin interactions and led to healing of pseudoporphyria bullous lesions. Finally we highlight the prominent role of UV-exposure in PP elicitation thus a good photoprotection is essential for all patients with pseudoporphyria.

Health related quality of life in patients in dialysis after renal graft loss and effect of gender.

BACKGROUND: An increasing number of dialysis patients have returned to dialysis after renal graft loss, and the transition in disease state could likely be associated with reduced health related quality of life (HRQOL). Furthermore, gender differences in HRQOL have been observed in dialysis and kidney transplanted patients, but whether transition in disease state affects HRQOL differently in respect to gender is not known. The aims of this study were to compare HRQOL in dialysis patients with graft loss to transplant naïve dialysis patients, and to explore possible gender differences. METHODS: In a cross-sectional study, HRQOL was measured in 301 prevalent dialysis patients using the Kidney Disease and Quality of Life Short Form version 1.3. Adjusted comparisons were made between dialysis patients with previous graft loss and the transplant naïve patients. Multiple linear regression analyses were performed with HRQOL as outcome variables. Interaction analyses using product terms were performed between gender and graft loss. HRQOL was analysed separately in both genders. RESULTS: Patients with renal graft loss (n = 50) did not experience lower HRQOL than transplant naïve patients after multiple adjustments. Among patients with graft loss, women (n = 23) reported lower HRQOL than men (n = 27) in the items physical function (40 vs. 80, p = 0.006), and effect of kidney disease (49 vs. 67, p = 0.017). Women with graft loss reported impaired kidney-specific HRQOL compared to transplant naïve women (n = 79) in the items effect of kidney disease (50 vs. 72, p = 0.002) and cognitive function (80 vs. 93, p = 0.006), and this observation persisted after multiple adjustments. Such differences were not apparent in the male counterparts. CONCLUSIONS: Patients who resumed dialysis after renal graft loss did not have lower HRQOL than dialysis patients not previously transplanted. However, losing graft function was associated with reduced HRQOL in females, and important interactions were identified between graft loss and gender. This needs to be further explored in prospective studies.

Chronic kidney disease in patients with renal cell carcinoma.

Renal cell carcinoma (RCC) is diagnosed in over 65,000 Americans annually, and earlier detection and advances in surgical techniques have resulted in improved oncological outcomes. Given that diabetes and hypertension are independent risk factors for the development of RCC, it is not surprising that diabetic nephropathy or hypertensive nephrosclerosis are commonly encountered in these patients. Data support that at least one third of the 300,000 kidney cancer survivors in the United States have or will develop CKD; however, the effect of CKD in this clinical setting has largely evaded the attention of the medical community. It is likely that CKD which develops from postsurgical therapy for RCC may limit long-term outcomes by increasing the risk for cardiovascular morbidity and mortality. To further improve the clinical outcomes for kidney cancer patients, better recognition and management of CKD, which requires coordination among urologists, pathologists, and nephrologists, will be essential.