Renal function and systolic blood pressure in very-low-birth-weight infants 1–3?years of age

Background

Preterm very-low-birth-weight (PT-VLBW) infants are at risk of an elevated systolic blood pressure (SBP) in infancy and adulthood; however, the pathogenesis remains unclear. Altered renal development or function may be associated with increased SBP, but their contribution in PT-VLBW is unknown.

Methods

We determined renal function and its relationship to SBP in three groups of PT-VLBW at 1, 2, and 3?years of age, using serum cystatin-C to calculate the estimated glomerular filtration rate (eGFR).

Results

Cystatin-C levels decreased from 0.84?±?0.2 (SD) within the 1-year group to 0.70?±?0.1?mg/l (±SD; P?<?0.001) at 3?years and were unrelated to gender, fetal growth, and neonatal indomethacin exposure. eGFR rose from 121?±?59 in the 1-year group to 138?±?21?ml/min·1.73?m² (P?<?0.001) at 3?years. At 1?year, cystatin-C levels decreased with increasing SBP (P?<?0.007), and infants with SBP ≥?90th% had lower cystatin-C and higher eGFR (P?<?0.05). At 3?years, infants with lower birth weight (P?<?0.03) and gestational age (P?=?0.06) had reduced eGFR.

Conclusions

Preterm very-low-birth-weight infants demonstrate increasing renal function with advancing age. An elevated SBP and eGFR at 1?year suggests dysfunctional renal autoregulation and hyperfiltration, which may alter subsequent renal function and contribute to the lower eGFR seen at 3?years in infants with the lowest birth weight and gestational age.     

Overweight and obesity accelerate the progression of IgA nephropathy: prognostic utility of a combination of BMI and histopathological parameters

Background

Although more than 40?years have passed since IgA nephropathy (IgAN) was first reported, predicting the renal outcome of individual IgAN patients remains difficult. Emerging epidemiologic evidence indicates that overweight and obesity are risk factors for end-stage renal disease. We aimed to elucidate the outcome of overweight IgAN patients and improve our ability to predict the progression of IgAN based on a combination of body mass index (BMI) and histopathological parameters, including maximal glomerular area (Max GA).

Methods

Forty-three adult IgAN patients whose estimated glomerular filtration rate was ≥50?ml/min/1.73?m² were enrolled in this study. Renal biopsy specimens were evaluated according to the Oxford classification of IgAN. A Kaplan–Meier analysis and the multivariate Cox proportional hazards method were used to evaluate 10-year kidney survival and the impact of covariates. The ability of factors to predict the progression of IgAN was evaluated by their diagnostic odds ratio (DOR).

Results

A BMI ≥25?kg/m² was found to be an independent predictor of a ≥1.5-fold increase in serum creatinine value (DOR 7.4). The combination of BMI ≥25?kg/m², Max GA ≥42,900?μm², and presence of mesangial hypercellularity (Oxford M1) optimally raised predictive power for disease progression of IgAN (DOR 26.0).

Conclusion

A combination of BMI ≥25?kg/m², the Oxford classification M1, and a Max GA ≥42,900?μm² can serve as a predictor of long-term renal outcome of IgAN.     

Complete remission within 2 years predicts a good prognosis after methylprednisolone pulse therapy in patients with IgA nephropathy

Background

Pozzi et al. reported the effectiveness of steroid pulse therapy (Pozzi??s regimen) in IgA nephropathy (IgAN). The present study was performed to clarify the predictive factors for IgAN patients treated with Pozzi??s regimen.

Methods

One hundred nine IgAN patients treated by Pozzi??s regimen were observed for up to 112.6 (median 39.7) months, and remission of proteinuria (PR) and disappearance of urinary abnormalities [complete remission (CR)] after Pozzi??s regimen were analyzed. Predictive factors for the glomerular filtration rate (GFR) slopes for up to 5?years were analyzed among 81 patients who were observed for at least 2?years. The outcome of a 50?% increase in sCr was compared between the CR and non-CR groups within 2?years.

Results

Cumulative PR and CR rates increased rapidly until 2?years (54.5 and 46.8?% at 2?years), and then slowly but steadily up to 6?years (72.8 and 66.4?% at 6?years). Baseline characteristics of the CR and non-CR groups within 2?years were similar except for proteinuria. GFR slope was steeper in the non-CR group than in the CR group (?2.44?±?5.12 vs. ?0.32?±?3.34?ml/min/1.73?m²/year). On multivariate analysis, sex and CR within 2?years were associated with GFR slope. Kaplan-Meier analysis demonstrated a better survival rate in CR group patients without a 50?% increase in sCr (p?=?0.024).

Conclusions

Among IgAN patients treated with Pozzi??s regimen, CR within 2?years predicts a good prognosis.     

The features in IgA-dominant infection-related glomerulonephritis distinct from IgA nephropathy: a single-center study

Background

IgA-dominant infection-related glomerulonephritis (IgA-IRGN) is a unique form of IRGN, which needs to be distinguished from IgA nephropathy (IgAN).

Methods

Thirteen patients with IgA-IRGN (IgA-IRGN group) and 122 with IgAN (IgAN group) were selected from 1788 patients who underwent kidney biopsy between 2000 and 2015 in Kitano Hospital. Data selected included clinical and serological parameters; light and electron microscope findings; immunofluorescence findings; and prognostic parameters like renal and overall survival and creatinine increase by >?50%. In addition, a 26-patient IgAN cohort (matching-IgAN), matching with IgA-IRGN group with respect to age, sex, estimated glomerular filtration rate (eGFR), and proteinuria was segregated for comparison.

Results

Compared to IgAN group, IgA-IRGN group were older, had lower hemoglobin, higher CRP, lower eGFR, heavier proteinuria, lower serum albumin, and higher serum IgG and IgA levels (p?<?0.05). Endocapillary hypercellularity, deposition of immune complexes along the glomerular capillary wall, and subendothelial and subepithelial electron dense deposits were more frequently observed (p?<?0.05); and they were more susceptible to renal dysfunction and poorer prognosis. After propensity score-matching, serum albumin was significantly lower in the IgA-IRGN group. Significantly subendothelial and subepithelial deposits were frequently observed in this group. Matching-IgAN group showed relatively advanced sclerotic lesions with more global sclerosis and fibrous crescent.

Conclusion

Local inflammation involved glomerular capillary wall in IgA-IRGN, in contrast to relatively chronic and sclerotic renal lesion in IgAN, might result in poorer prognosis in former, even under indistinguishable condition of deteriorated renal function and proteinuria.

     

Nephrotic syndrome in Kawasaki disease: a report of three cases

Background

Renal manifestations are rare in Kawasaki disease (KD). Acute renal failure with tubular necrosis, tubulointerstitial nephritis and renovascular hypertension have been reported in KD, but only one case of a patient with KD associated with nephrotic syndrome (NS) has been reported to date, with the patient improving on steroid therapy but dying from coronary aneurysm.

Methods

We report the cases of three children, aged 4, 4.5 and 8?years, respectively, who presented with typical KD symptoms (high fever, diffuse maculopapular rash, conjunctivitis, peripheral oedema, cervical adenopathies and high C reactive protein levels) and developed NS.

Results

Patient 1 had a haemodynamic shock due to cardiac dysfunction and transient renal failure. Ten days later, he developed a NS which spontaneously disappeared 1 week later. Patient 2 had a NS on admission with normal plasma creatinine and no haematuria. Proteinuria disappeared within 10?days. Patient 3 developed NS 5?days after onset with a moderate increase in plasma creatinine. Proteinuria disappeared within 2?weeks. All three patients were treated with intravenous immunoglobulins, antibiotic therapy and aspirin, but none of them received steroid therapy. To date, all three patients have maintained long-term remission.

Conclusions

In conclusion, proteinuria with NS may develop during the acute phase of KD with persistent remission occurring without steroid therapy.     

Histologically advanced IgA nephropathy treated successfully with prednisolone and cyclophosphamide

Background

No definitive therapeutic consensus has been established for progressive immunoglobulin A nephropathy (IgAN).

Methods

We retrospectively investigated 35 patients with histologically advanced IgAN. The patients were divided into two groups: 27 received prednisolone and cyclophosphamide (PSL+CPA group) and 8 received supportive treatment (control group). The initial doses of PSL and CPA were 30?mg/day and 50?mg/day, respectively. PSL was tapered to 2.5?mg/day over 2 years and CPA was discontinued at 6 months.

Results

In the control group, mean follow-up duration was 22.9 months, renal progression rate was ?20.9 × 10<συπ>?3?dl/mg per month, and all patients developed endstage renal disease within 5 years. In the PSL+CPA group, mean follow-up duration was 64.3 months, renal progression rate was ?1.5 × 10<συπ>?3?dl/mg per month, and renal survival at 5 years was 89.8%. Renal prognosis was markedly improved in the PSL+CPA group compared with the control group. The patients in the PSL+CPA group were divided into two subgroups according to baseline serum creatinine (<2?mg/dl or ≥2?mg/dl); renal survival in the two subgroups was similar (84.4% versus 100% at 5 years). Adverse effects of PSL+CPA were minimal and mild.

Conclusions

It is possible that PSL+CPA therapy safely improved the renal prognosis of patients with severe IgAN who would otherwise have required dialysis therapy within 5 years. However, a prospective, multicenter clinical trial is required to prove the effects and safety of this treatment.

     

Extra-uterine renal growth in preterm infants: Oligonephropathy and prematurity

Background

Nephron number in humans is determined during fetal life. The objective of this study was to investigate the effects of preterm birth on nephron number using renal volume as a surrogate for nephron number.

Methods

This observational study was conducted over 12 months in a tertiary perinatal center. Preterm babies less than 32 weeks of gestation were recruited and followed until discharge. Term infants were recruited for comparison. The babies underwent renal sonography and renal function measurements at 32 and 38 weeks corrected age. The primary outcome measurement was total kidney volume at 38 weeks and the secondary outcome was estimated glomerular filtration rate (eGFR).

Results

Forty-four preterm infants and 24 term infants were recruited. At 38 weeks corrected age, premature infants had lower total kidney volume than term infants (21.6?±?5.7 vs. 25.2?±?5.7 ml; p?=?0.02) and a significantly lower eGFR (73.6 [IQR 68.1–77.6] vs. 79.3 [IQR 72.5–86.6] ml·min^?1·1.73 m^?2; p?=?0.03). There was a significant correlation between total kidney volume and eGFR in premature and term babies.

Conclusions

Premature infants have smaller kidney volume and likely decreased nephron number and lower estimated glomerulofiltration rate relative to infants born at term.     

Utility of the Japanese GFR estimation equation for evaluating potential donor kidney function

Background

In Japan, the number of living kidney transplantations has increased each year, and an accurate evaluation of renal function must be conducted before donation to minimize the risk to donors. Recently, the Japanese Society of Nephrology issued a new equation for estimating glomerular filtration rate (eGFR) in Japanese people. This study compared the accuracy of eGFR and creatinine clearance (Ccr) values with that of inulin clearance (Cin) for assessing renal function in kidney donors.

Methods

Clinical data were analyzed for 85 potential living kidney donors who had undergone routine measured GFR (mGFR) and Ccr measurements from October 2006 to November 2008 at a single center. Inulin clearance, representing the mGFR, was determined by standard method. The eGFR was calculated as: eGFR = 194 × Scr^?1.094 × Age^?0.287 (for females, ×0.739).

Results

Mean mGFR was 96.1 ± 14.7 (range 67.8–126.8); mean eGFR, 72.6 ± 12.7 (range 50.1–107.1); and mean Ccr, 117.3 ± 22.4 (range 35.1–170.1), in units of ml/min/1.73 m² for each. Relative to mGFR, the correlation coefficient for Ccr was 0.496, and the mean difference between the two values was 21.1 ml/min/1.73 m² (23.2%), with a root-mean square error (RMSE) of 19.6. The correlation coefficient between eGFR and mGFR was 0.502, and the mean difference between the two values was ?23.5 (23.7%), with a RMSE of 11.0. Bland–Altman plots showed that Ccr overestimated mGFR in 90.6% of cases, whereas eGFR underestimated mGFR in 95.3% of cases.

Conclusion

Ccr and eGFR values did not accurately estimate mGFR in Japanese living kidney donors.     

Treatment outcome of late steroid-resistant nephrotic syndrome: a study by the Midwest Pediatric Nephrology Consortium

Background

Idiopathic nephrotic syndrome (NS) in children is classified as steroid sensitive or steroid resistant. Steroid sensitivity typically portends a low risk of permanent renal failure. However, some initially steroid-sensitive patients later develop steroid resistance. These patients with late steroid resistance (LSR) are often treated with immunosuppressant medications, but the effect of these additional drugs on the long-term prognosis of LSR is still unknown.

Methods

A retrospective chart review was performed on patients diagnosed with idiopathic NS and subsequent LSR during the 8-year study period from 2002 up to and including 2009, with a minimum of 2 years of follow-up. Primary outcome measures were proteinuria and renal function.

Results

A total of 29 patients were classified as having LSRNS. The majority of patients received treatment with calcineurin inhibitors and/or mycophenolate mofetil. Seven patients received three or more non-steroid immunosuppressant medications. Sustained complete or partial remission was achieved in 69 % of patients. Three developed end-stage renal disease, and all others maintained normal renal function. There were 13 episodes of serious adverse events, none of which were fatal or irreversible.

Conclusion

Most patients with LSRNS responded to immunosuppressive therapy by reduction or resolution of proteinuria and preservation of renal function. The results suggest that immunosuppressive treatment is a viable option in NS patients who develop LSR.     

Tonsillectomy reduces recurrence of IgA nephropathy in mesangial hypercellularity type categorized by the Oxford classification

Background

In patients with IgA nephropathy (IgAN), recurrence after steroid pulse therapy is associated with reduced renal survival. However, the predictors of recurrence have not yet been clarified.

Methods

All patients who received 6-month steroid pulse therapy from 2004 to 2010 in our four affiliated hospitals and achieved a reduction of proteinuria to <0.4 g/day 1 year after treatment were retrospectively evaluated. The primary outcome was proteinuria ≥1.0 g/day during follow-up or additional antiproteinuric therapy. Two histological classifications were evaluated, the Oxford Classification with a split system and Japanese histological grades (HGs) with a lumped system.

Results

During a median follow-up of 3.4 years, 27 (26.7 %) of the 101 patients showed recurrence. Multivariate analysis showed that HG was the only significant predictor of recurrence, with HG 2+3+4 vs HG 1 having a hazard ratio of 7.38 (95 % confidence interval 1.52–133). Furthermore, in patients with mesangial hypercellularity according to the Oxford Classification, cumulative rate of recurrence-free survival was greater in patients with steroid therapy plus tonsillectomy compared with those who received steroid therapy alone (Log-rank test, P = 0.022). However, this association was not observed in patients without mesangial hypercellularity.

Conclusions

HG is a novel predictor of recurrence after steroid pulse therapy in patients with IgAN. Moreover, the combination of steroid pulse therapy plus tonsillectomy may indicate a lower risk of recurrence in patients with mesangial hypercellularity, as defined by the Oxford Classification.

     

Race-specific relationship of birth weight and renal function among healthy young children

Background

Low birth weight is associated with diminished renal function. However, despite African Americans being at increased risk of low birth weight and chronic kidney disease, little is known about the association between birth weight and renal function in diverse groups. We examined racial differences in the relationship of birth weight and renal function among healthy young children.

Methods

Birth weight and serum creatinine data were available on 152 children (61.8% African American; 47.4% female) from a birth cohort. Estimated glomerular filtration rate (eGFR) was calculated using the bedside Schwartz equation and gender- and gestational-age-adjusted birth weight Z-scores using the US population as a reference. Race-specific linear regression models were fit to estimate the association between birth weight Z-score and eGFR.

Results

Mean age was 1.5?±?1.3?years at first eGFR measurement. African Americans had lower eGFR than non-African Americans (median eGFR?=?82 vs. 95?ml/min per 1.73?m²; p?=?0.06). Birth weight was significantly and positively associated with eGFR among African American (p?=?0.012) but not non-African American children (p?=?0.33).

Conclusions

We provide, for the first time, evidence suggesting that birth weight is associated with renal function in African American children. Future work is needed to determine if prenatal programming helps explain racial disparities in adult health.     

KIM-1 expression predicts renal outcomes in IgA nephropathy

Background

Kidney injury molecule-1 (KIM-1) is a sensitive biomarker for proximal tubular injury. Recently, a few studies have shown that urinary KIM-1 has clinical implications in IgA nephropathy (IgAN). We performed this study to determine whether tissue KIM-1 has clinical implications for predicting long-term outcome and whether urinary KIM-1 is correlated with tissue KIM-1 and kidney injury in IgAN patients.

Methods

We assessed the prognostic prediction capability of tissue KIM-1 expression in 69 adult patients with IgAN retrospectively. Renal biopsies from all patients were scored by a pathologist who was blinded to the clinical data for the pathologic variables. The primary outcome was the composite of a 50 % reduction in eGFR or end-stage renal disease. Tissue KIM-1 expression was assessed semiquantitatively by counting the stained tubules per 100× power field; 0 tubule indicates grade 0; 1–5 tubules, grade 1; 6–10 tubules, grade 2; and more than 10 tubules, grade 3. Comparing urinary KIM-1 and tissue KIM-1 expression, 50 consecutive IgAN patients were prospectively enrolled to measure urinary KIM-1 levels and examine their biopsy specimens by KIM-1 immunohistochemistry.

Results

Univariate analysis showed that tissue KIM-1 expression was associated with the renal outcome in IgAN. Multivariate regression analysis, as the relationship of tissue KIM-1 with prognosis, was consistent. Proteinuria at biopsy and tissue KIM-1 grade 3 were shown to have a prognostic value. The concentration of urinary KIM-1/Cr in patients with IgAN was significantly higher than that in the normal controls.

Conclusion

Tissue KIM-1 expression is an independent predictor of adverse renal outcomes in IgA nephropathy patients.     

Primary membranoproliferative glomerulonephritis on the decline: decreased rate from the 1970s to the 2000s in Japan

Background

A prolonged change in the rate of primary membranoproliferative glomerulonephritis (MPGN) was identified using a Japanese database of renal biopsies.

Methods

We retrospectively investigated 6,369 renal biopsies that were performed between 1976 and 2009. Primary MPGN patients were selected, and the clinical and pathological findings were examined. We also statistically analyzed the changing rate of the onset of primary MPGN according to each decade.

Results

Seventy-nine cases with primary MPGN (1.2 % of total biopsies) were diagnosed. The age of the patients ranged from 6–79 years (average 34.6 years). There were 24 children and 55 adults, including 37 male and 42 female patients. Thirty-six cases of primary MPGN (45.6 %) showed nephrotic syndrome—8 childhood and 28 adult cases. In the pathological classification of 44 samples using electron microscopy, 29 cases were MPGN type I, 1 case was MPGN type II, and 14 cases were MPGN type III. The secular change of the rate of primary MPGN onset showed a statistically significant reduction from the 1970s to the 2000s. The rate of primary MPGN onset in the child population also significantly decreased, but not in the adult population. Among the clinical parameters, disease severity and prognosis remained unchanged. Regarding treatment in recent years, steroid pulse therapy became more available but the administration of warfarin and anti-platelet drugs significantly decreased.

Conclusion

We concluded that the rate of total primary MPGN and that of pediatric patients with primary MPGN decreased.     

The impact of serum uric acid reduction on renal function and blood pressure in chronic kidney disease patients with hyperuricemia

Background

Febuxostat is tolerable in chronic kidney disease (CKD) patients with hyperuricemia. However, the long-term effect of lowering uric acid with febuxostat on renal function and blood pressure has not been elucidated.

Methods

This was a 2 years retrospective observational study. 86 CKD patients with hyperuricemia who continued with allopurinol (allopurinol group, n?=?30), switched from allopurinol to febuxostat (switched group, n?=?25), or were newly prescribed febuxostat (febuxostat group, n?=?31) were included in this study. Serum uric acid, estimated glomerular filtration rate (eGFR), blood pressure, and urinary protein were analyzed. Moreover, the impact of serum uric acid reduction on renal function and blood pressure was assessed.

Results

Serum uric acid in the switched and febuxostat groups was significantly reduced at 6 months (switched group; 8.49?±?1.32–7.19?±?1.14 mg/dL, p?<?0.0001, febuxostat group; 9.43?±?1.63–6.31?±?0.90 mg/dL, p?<?0.0001). In the allopurinol group, serum uric acid was increased (6.86?±?0.87–7.10?±?0.85 mg/dL, p?=?0.0213). eGFR was significantly increased (35.2?±?12.8–37.3?±?13.9 mL/min/1.73 m², p?=?0.0232), while mean arterial pressure (93.1?±?10.8–88.2?±?9.5 mmHg, p?=?0.0039) was significantly decreased at 6 months in the febuxostat group, resulting in the retention of eGFR for 2 years.

Conclusions

The impact of serum uric acid reduction might have beneficial effects on CKD progression and blood pressure. However, a large prospective study is needed to determine the long-term efficacy of febuxostat therapy in CKD patients with hyperuricemia.

     

The clinical relevance of plasma CD147/basigin in biopsy-proven kidney diseases

Background

Precise understanding of kidney disease activity is needed to design therapeutic strategies. CD147/basigin is involved in the pathogenesis of acute kidney injury and renal fibrosis through inflammatory cell infiltration. The present study examined the clinical relevance of CD147 in biopsy-proven kidney diseases that lead to the progression of chronic kidney disease.

Methods

Kidney biopsy specimens and plasma and urine samples were obtained from patients with kidney diseases, including IgA nephropathy (IgAN), Henoch–Schönlein purpura nephritis (HSPN), diabetic kidney disease (DKD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN), who underwent renal biopsy between 2011 and 2014. Plasma and urinary CD147 levels were measured and evaluated for their ability to reflect histological features. Disease activity of IgAN tissues was evaluated according to the Oxford classification and the Japanese histological grading system.

Results

In biopsy tissues, CD147 induction was detected in injured lesions representing renal inflammation. Plasma CD147 values correlated with eGFR in patients with inflammation-related kidney diseases such as IgAN, HSPN, and DKD. Particularly in IgAN patients, plasma CD147 levels were correlated with injured regions comprising more than 50% of glomeruli or with tubular atrophy/interstitial injury in biopsy tissues. Proteinuria showed a closer correlation with urinary values of CD147 and L-FABP. Of note, plasma and urinary CD147 levels showed a strong correlation with eGFR or proteinuria, respectively, only in DKD patients.

Conclusion

Evaluation of plasma and urinary CD147 levels might provide key insights for the understanding of the activity of various kidney diseases.

     

Comparison between steroid pulse therapy alone and in combination with tonsillectomy for IgA nephropathy

Purpose

To the best of our knowledge, no study has compared intermittent steroid pulse therapy, according to Pozzi’s regimen, with versus without tonsillectomy.

Methods

In this retrospective cohort analysis, we compared clinical findings, histological findings according to the Oxford classification, and complete remission rates (RR), defined in terms of urinary protein excretion (U-Prot <0.3 g/g creatinine) and urinary red blood cell count (U-RBC <5/high-power field), after 1 year of treatment in patients with IgA nephropathy (IgAN), who received tonsillectomy with steroid pulse therapy (TSP group, n = 26) or steroid pulse therapy alone (SP group, n = 15).

Results

The baseline clinical and histological characteristics did not differ between the two groups. The RR for U-Prot analyzed by the Kaplan–Meier method did not differ between the groups (76.9 vs. 53.3 %). However, the RR for U-RBC was significantly higher in the TSP than in the SP group (88.4 vs. 33.3 %, log-rank test; P = 0.0008). The RRs for U-Prot and U-RBC were significantly higher in the TSP group than in the SP group (69.2 vs. 13.3 %, log-rank test; P = 0.0019). Cox’s regression analysis showed that combination therapy was associated with higher RR (odds ratio, 12.5; 95 % confidence interval, 2.91–86.7; P = 0.0002).

Conclusions

Tonsillectomy combined with steroid pulse therapy achieved higher RR after 1 year of treatment, compared with steroid pulse monotherapy in patients with IgAN. The long-term effects on renal survival should be analyzed in further studies.     

Deferasirox-induced renal impairment in children: an increasing concern for pediatricians

Background

Deferasirox (DFX) is an oral iron chelator with an established dose-dependent efficacy in transfusion-related iron overload. Whereas emerging long-term data confirm the safety of the drug, with transient moderate elevation of serum creatinine level, several authors have reported renal tubular dysfunction. The aim of this study was to evaluate tubular and glomerular function before and after the initiation of DFX therapy in a pediatric patient population.

Methods

Ten children (4 girls, mean age 12.4?±?3.9?years) enrolled in a routine blood transfusion program were treated with 24.8?±?9.6?mg/kg per day of DFX, and renal function was assessed before and 17.2?±?8.9?months after the initiation of DFX therapy.

Results

Prior to treatment with DFX, all patients had a normal glomerular function rate (GFR) (125?±?15?ml/min per 1.73?m²) and normal tubular function. Following the initiation of DFX therapy, the GFR decreased by approximately 20?% with one patient with a GFR of?<80?mL/min per 1.73?m² and seven patients with a GFR of?<100?mL/min per 1.73?m². Two patients experienced a generalized proximal tubular dysfunction whereas nine patients presented at least one sign of proximal tubular dysfunction.

Conclusions

Renal toxicity is a frequent adverse event of DFX treatment, presenting as both glomerular and proximal dysfunction. A routine renal assessment is therefore required to prevent chronic kidney disease that may result from prolonged tubular injury.     

Long-term safety and efficacy of renin–angiotensin blockade in atherosclerotic renal artery stenosis

Purpose

The activation of the renin?Cangiotensin?Caldosterone system caused by renal ischaemia in atherosclerotic renal artery stenosis (ARAS) may be responsible for serious cardiovascular and renal consequences. The aim of the study was to assess the long-term safety, tolerability and outcomes of the use of angiotensin I-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) in patients with ARAS.

Methods

Thirty-six patients with angiographically defined ARAS (managed either with revascularization or only with medical treatment) were prospectively assessed for the safety, tolerability and outcomes of the use of ACEis or ARBs.

Results

The mean period of follow-up was 88.9?±?37.8?months. A statistically significant reduction in systolic and diastolic blood pressure was recorded over time (P?P?=?0.03). Mean time from diagnosis/intervention to end-stage renal disease for the cohort of 36 patients was 165.38?±?13.62?months. Mean overall patient survival was 135.36?±?15.25?months, with fourteen deaths (38.8%) occurring during the observational period. ACEi/ARB therapy was discontinued transiently in only 4 subjects.

Conclusions

The use of ACEis/ARBs is safe and effective in patients with ARAS independently of any parameters.     

Renal function and adaptive changes in patients after radical or partial nephrectomy

Introduction

Renal function after renal surgery depends on the volume of renal parenchyma loss and improves in the postoperative period. However, the knowledge on kidney function after radical (RN) and partial (PN) nephrectomy is still insufficient. The aim of this study is to analyze the global renal function and compensatory hyperfunction of the non-operated kidney in patients with renal cancer after RN or PN.

Methods

Fifty-one patients of mean age 62.2?years with renal cancer were included. Thirty-three RN and eighteen PN were performed. We measured creatinine serum concentrations, and we estimated glomerular filtration rate (eGFR) preoperatively and postoperatively at two time intervals: 3 and 12?months after surgery. Additionally, we assessed effective renal plasma flow (ERPF) in dynamic scintigraphy preoperatively and 12?months after surgery.

Result

At the baseline, all mean measured values were comparable in RN and PN groups (P?>?0.05). Three?months after surgery, creatinine level increased in both groups, more remarkably in RN group (128?mmol/l vs. 95?mmol/l; P?2 vs. 70?ml/min/1.73?m²; P?P?>?0.05). The mean ERPF of the operated kidney in PN group decreased by 24.7% (149?ml/min).

Conclusion

The deterioration of renal function after partial nephrectomy is nearly insignificant clinically. In 1-year postoperative observation, the renal function does not improve. This causes potential compensatory mechanisms to be insufficient.     

Remission of nephrotic syndrome diminishes urinary plasmin content and abolishes activation of ENaC

Background

Urinary plasmin activates the epithelial Na⁺ channel (ENaC) in vitro and may possibly be a mechanism of sodium retention in nephrotic syndrome (NS). This study used a paired design to test the hypothesis that remission of NS is associated with a decreased content of urinary plasmin and reduced ability of patients’ urine to activate ENaC.

Methods

Samples were collected during active NS and at stable remission from 20 patients with idiopathic NS, aged 9.1?±?3.2 years. Plasminogen–plasmin concentration was measured with an enzyme-linked immunosorbent assay. Western immunoblotting for plasminogen–plasmin was performed in paired urine samples. The patch clamp technique was used to test the ability of urine to evoke an inward current on collecting duct cells and human lymphocytes.

Results

The urinary plasminogen–plasmin/creatinine ratio was 226 [95 % confidence interval (CI) 130–503] μg/mmol in nephrotic urine versus 9.5 (95 % CI 8–12) μg/mmol at remission (p?<?0.001). Western immunoblotting confirmed the presence of active plasmin in urine collected during active NS, while samples collected at remission were negative. Nephrotic urine generated an inward amiloride- and α₂-anti-plasmin- sensitive current, whereas the observed increase in current in urine collected at remission was significantly lower (201?±?31 vs. 29?±?10 %; p?=?0.005).

Conclusions

These findings support the hypothesis that aberrantly filtered plasminogen–plasmin may contribute to ENaC activation and mediate primary renal sodium retention during active childhood NS.