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.     

Use of the ImmuKnow assay to evaluate the effect of alemtuzumab-depleting induction therapy on cell-mediated immune function after renal transplantation

Background

Good outcomes after renal transplantation are dependent on effective immunosuppression while minimizing infection. Alemtuzumab (Campath or Campath-1H) is an anti-CD52 humanized monoclonal IgG1 antibody which induces rapid and sustained depletion of circulating lymphocytes and has been effectively used as an immunosuppressant in post-transplant induction therapy.

Methods

We used the ImmuKnow assay to compare cell-mediated immune function in renal transplant patients treated with alemtuzumab or with conventional immunosuppressive tri-therapy. The ImmuKnow method determines the levels of adenosine triphosphate (ATP) released from CD4 cells following stimulation with a mitogen.

Results

We showed a statistically significant difference in the distribution of outcome after transplantation between the conventional and the Campath groups (P = 0.010). A significantly higher number of patients treated with alemtuzumab induction therapy were stable after transplantation compared to those treated with conventional immunosuppressive tri-therapy (96.6 vs. 75.7 %). ATP values were significantly higher in the conventional group compared to the Campath group at 180 days after transplantation (P < 0.001). ATP levels did not change significantly over time in clinically stable kidney recipients treated with alemtuzumab induction therapy (P = 0.554).

Conclusions

The ImmuKnow assay is a useful tool for evaluating the global immune response in alemtuzumab-treated renal transplant patients. Alemtuzumab-depleting induction therapy remains effective for at least 180 days.     

Rituximab treatment combined with methylprednisolone pulse therapy and immunosuppressants for childhood steroid-resistant nephrotic syndrome

Background

Calcineurin inhibitors (CIs) with/without intravenous methylprednisolone pulse therapy (MPT) constitute the standard treatment for childhood-onset, steroid-resistant nephrotic syndrome (SRNS). However, some patients fail to achieve remission. We treated SRNS patients resistant to CIs and MPT with additional rituximab combined with MPT and immunosuppressive agents.

Methods

Ten patients (aged 2–14 years) with CI- and MPT-resistant SRNS were enrolled. Patients were administered rituximab (1–4 doses; 375 mg/m²) followed by MPT (30 mg/kg/day of methylprednisolone for 3 consecutive days) once every 2–4 weeks until complete remission (CR). We analyzed clinical outcome and safety.

Results

Six patients received a single dose of rituximab, 2 received two doses, and 2 received four doses. Seven patients achieved CR, 1 achieved partial remission, and 2 showed no response. Although 2 patients with no response progressed to end-stage renal failure, 7 patients with CR preserved normal renal function without proteinuria at the last observation. There were two serious adverse events.

Conclusions

Additional rituximab combined with conventional MPT and immunosuppressive agents is a promising option for overcoming refractory SRNS. Aggressive B cell suppression by rituximab may ameliorate resistance to conventional treatments and a cocktail of other immunosuppressive agents, such as CIs, MMF, mizoribine, may be beneficial. However, as intense immunosuppression may cause serious adverse events, further evaluation is necessary.     

Successful management of factor IX inhibitor-associated nephrotic syndrome in a hemophilia B patient

Background

Nephrotic syndrome (NS) is a recognized complication of immune tolerance induction (ITI) therapy, a treatment strategy used to treat inhibitors in patients with hemophilia B receiving factor IX concentrate.

Case diagnosis/treatment

We present a 4-year-old boy with hemophilia B and an inhibitor who underwent ITI, and developed NS 19 months into this therapy. A percutaneous renal biopsy was safely performed with factor IX (FIX) concentrate administration both preceding and following the procedure. The patient’s inhibitor level had increased to 1.4–1.6 Bethesda Units just prior to the onset of proteinuria. Histology confirmed segmental membranous nephropathy (MGN). The patient was continued on FIX concentrate as ITI and also received 4 weekly doses of rituximab and ongoing immunosuppression with mycophenolate mofetil. This resulted in the complete resolution of his inhibitor and his NS. He continues with a modified ITI regimen and remains inhibitor-free without proteinuria >12 months post-biopsy.

Conclusions

Hemophilia B patients undergoing ITI should be regularly screened for NS. At first detection of proteinuria, with proper precautions, a percutaneous kidney biopsy can be performed safely in patients with low levels of inhibitor. Our patient had segmental MGN with complete remission of NS.     

Nonfunction of the ECT2 gene may cause renal tubulointerstitial injury leading to focal segmental glomerulosclerosis

Background

Secondary focal segmental glomerulosclerosis (FSGS) follows congenital or acquired tubulointerstitial alterations such as in Dent??s disease, Lowe syndrome, and reflux nephropathy. Failure of adequate regeneration after tubulointerstitial injury, or abnormal tubulogenesis, can disturb intrarenal blood circulation, causing excessive glomerular filtration. The epithelial cell-transforming sequence 2 gene (ECT2) contributes to tight junction function in epithelial cells.

Methods

We encountered two patients with a nonfunctioning ECT2 genotype who later developed FSGS. Both developed proteinuria associated with acute renal failure in early childhood.

Results

Renal biopsy specimens showed marked tubulointerstitial nephritis at the onset of proteinuria, later progressing to FSGS consequent to tubulointerstitial injury. The patients did not respond to corticosteroids and attained only incomplete remission upon cyclosporine A administration. One patient received a maternal renal transplant with good function and no rejection.

Conclusions

ECT2 is important for tight junction function and maintenance of cell polarity. Nonfunction of this gene may cause renal tubulointerstitial injury, progressing to glomerular sclerosis.     

Expanding the phenotype of proteinuria in Dent disease. A case series

Background

Dent disease is an X-linked recessive renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and progressive renal failure (MIM 300009). A recent case series identified four patients with CLCN5 mutations who presented with nephrotic-range proteinuria, histologic evidence of focal segmental and/or global sclerosis, and low molecular weight proteinuria.

Case-Diagnosis/Treatment

We characterize the clinical, genetic, and histopathological features of seven unrelated adolescent males with nephrotic-range proteinuria and CLCN5 mutations. Six patients underwent renal biopsy prior to assessing tubular proteinuria. All biopsied patients had either segmental sclerosis (3/6) or segmental increase in mesangial matrix (3/6). Five patients revealed some degree of foot process effacement, but only one patient biopsy revealed >50 % foot process effacement. The attenuated foot process effacement suggests the glomerulosclerosis is not due to a primary podocytopathy.

Conclusions

These data suggest that clinicians should consider a diagnostic evaluation for Dent disease in young males presenting with high-grade proteinuria.     

Eculizumab treatment for rescue of renal function in IgA nephropathy

Background

Immunoglobulin A (IgA) nephropathy is a chronic glomerulonephritis with excessive glomerular deposition of IgA1, C3 and C5b-9, which may lead to renal failure.

Case Diagnosis/Treatment

We describe the clinical course of an adolescent with rapidly progressive disease leading to renal failure in spite of immunosuppressive treatment. Due to refractory disease the patient was treated with eculizumab (anti-C5) for 3 months in an attempt to rescue renal function. Treatment led to clinical improvement with stabilization of the glomerular filtration rate and reduced proteinuria. Discontinuation of treatment led to a rapid deterioration of renal function. This was followed by a single dose of eculizumab, which again reduced creatinine levels temporarily.

Conclusions

Early initiation of eculizumab therapy in patients with progressive IgA nephropathy may have a beneficial effect by blocking complement-mediated renal inflammation.     

The role of albuminuria in the follow-up of HIV-infected pediatric patients

Background

In HIV-infected adults, elevated albumin has been associated with increased inflammatory activity, HIV-related nephropathy, and type 2 diabetes. Data on albuminuria in HIV-infected children are very scarce, and guidelines do not include routine determination of urinary albumin/creatinine ratio in this population.

Methods

We performed a cross-sectional study in a cohort of HIV-infected pediatric patients. Urinary protein/creatinine and albumin/creatinine ratios and hematuria were determined from at least three morning urine samples, and glomerular filtration rate (GFR) was estimated from creatinine levels. Persistent renal damage was defined according to the presence of at least two sequentially abnormal values in one of the parameters. The relationship between renal damage, HIV-related variables, and metabolic comorbidities (dyslipidemia, fat redistribution, glucose intolerance, hypertension) was investigated.

Results

Symptom-free renal damage was observed in 13 of 68 patients (19.1 %) and mainly consisted of persistent proteinuria (17.6 %); glomerular proteinuria was twice as prevalent as tubular proteinuria. GFR were normal in all cases. No relationship between renal markers and HIV-related variables or metabolic comorbidities was observed.

Conclusions

Mild proteinuria affected approximately one fifth of patients in our cohort. The determination of albuminuria allowed the differentiation between glomerular and tubular proteinuria, although no relationship with metabolic comorbidities was observed.     

Outcome of severe steroid-dependent nephrotic syndrome treated with mycophenolate mofetil

Background

Mycophenolate mofetil (MMF) is used as a steroid-sparing agent in pediatric nephrotic syndrome (NS). However, data about its long-term efficacy and safety is limited.

Methods

We report the long-term outcome of MMF therapy in 46 NS patients who remained steroid dependent (SD) despite previous treatment with levamisole and cyclophosphamide.

Results

After 1?year of MMF initiation, 32 (70?%) patients had reduced steroid requirement: 12 with decreased threshold dose and 20 were able to stop steroids. At follow-up of mean 3.56 (standard deviation?+?1.76) years, 25 (54?%) children required no further alternative immunosuppression (IS), having infrequent or no relapses, of which 14 stopped MMF after a mean 2.4 (standard deviation?+?0.9) years; 11 are continuing on MMF for a median of 2.25?years (range 1.33?C7.75?years). One patient had a psoriasis flare, and MMF was stopped. No other patient required permanent drug withdrawal due to side effects. The outcome of patients who did not require further alternate IS was significantly better than those who did, with 56?% vs. 10.5?%, respectively, being off regular medications at last follow-up.

Conclusions

We conclude that MMF therapy is safe in the long term and allows >50?% of severe SDNS patients to avoid further toxic IS.     

Insulin resistance in children with primary nephrotic syndrome and normal renal function

Background

Insulin resistance (IR) is an independent risk factor for atherosclerosis or cardiovascular events and renal function impairment. The aim of this study was to investigate IR in children with primary nephrotic syndrome (NS).

Methods

One-hundred and nineteen primary NS patients with normal renal function and 125 normal controls were studied. Fasting blood glucose, fasting serum insulin, and fasting serum C-peptide were measured. The Homa index of insulin resistance (HOMA-IR), Islet B cell function, and insulin sensitivity index were calculated. Correlations were assessed between HOMA-IR, fasting serum C-peptide, blood pressure, blood lipids, renal function, coagulation, clinical disease type, pathology and the early therapeutic effectiveness of high-dose glucocorticoids.

Results

There was no evidence of IR in the primary NS group. Although levels of fasting blood glucose, fasting serum insulin and fasting serum C-peptide were all within the normal ranges, fasting serum C-peptide was significantly higher compared to the controls. There was no disorder of carbohydrate metabolism in different hormone therapy efficacy and pathological diagnosis. Although IR was not detected, a significant increase in blood pressure, uric acid, blood lipids and coagulability was observed in the primary NS group.

Conclusion

A correlation observed between HOMA-IR, age, blood pressure, serum creatinine (Cr) and triglyceride may suggest that insulin sensitivity will emerge as renal disease progresses. Fasting serum C-peptide levels were increased in the primary NS group, suggesting that fasting serum C-peptide may be a protective factor.     

Early Postoperative Outcomes of Primary Bariatric Surgery in Patients on Chronic Steroid or Immunosuppressive Therapy

Background

Previous research suggests that patients on chronic steroids may be at an increased risk of postoperative morbidity after major surgery. We aimed to evaluate the prognostic impact of chronic use of steroid or immunosuppression on 30-day morbidity and mortality rates after primary bariatric surgery.

Methods

From American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database, we identified patients who underwent primary bariatric surgery between 2005 and 2013. Logistic regression was used to determine the prognostic impact of chronic use of steroid or immunosuppression on the 30-day postoperative outcomes.

Results

One thousand two hundred seventy seven steroid/immunosuppressant-dependent (SD) and 112,892 non-dependent (ND) patients were analyzed. SD patients had a higher baseline risk profile compared to ND patients. Thirty-day mortality rates for SD and ND patients were 0.55 and 0.11 %, respectively (P?<?0.001) which corresponds to an adjusted odds ration (OR) of 6.85 (95 % confidence interval (CI) 1.95–24.12). SD patients had a higher 30-day major morbidity compared to ND patients (5.01 versus 2.54 %; P?<?0.001, respectively). After adjustment, this translated into an OR of 2.21 (95 % CI 1.29–3.79). Among SD patients, there was no significant difference in 30-day major morbidity after gastric bypass compared to sleeve gastrectomy (OR?=?0.36; 95 % CI 0.08–1.66).

Conclusions

Chronic and active use of steroid or immunosuppressant medications is a strong predictor of 30-day postoperative morbidity and mortality following primary bariatric surgery. Among the steroid/immunosuppressant users, complication rates were similar for gastric bypass and sleeve gastrectomy patients. Further studies are needed to help guide the management or discontinuation of such medications in the perioperative period.

     

Annual incidence of persistent proteinuria in the general population from Ibaraki annual urinalysis study

Background

For a definitive diagnosis of chronic kidney disease, at least 2 consecutive positive results of proteinuria with an interval of >3 months are required. However, most previous reports were based on single-screening data.

Patients and methods

The subjects in this study were participants in an annual health examination held in Ibaraki, Japan, between 1993 and 2003. The follow-up duration with serial urinalysis for 3 years of patients who were negative for proteinuria in the initial year was 330,614 person-years in males and 687,381 person-years in females among 81,854 male and 155,256 female subjects. We evaluated the incidence and risk factor for the incidence of proteinuria and persistent proteinuria.

Result

The annual incidence of proteinuria and persistent proteinuria was 1.31 and 0.33 % in males and 0.68 and 0.14 % in females. Among the subjects without hypertension and diabetes, the annual incidence was 0.81 and 0.16 % in males and 0.37 and 0.06 % in females, respectively. Risk analysis indicated that hypertension in males [hazard ratio (HR) 2.052] and females (2.477), diabetes in males (3.532) and females (3.534) and reduced renal function in males (3.097) and females (2.827) were significant positive risks for development of persistent proteinuria.

Conclusion

By annual urinalysis screening of the general population, 1 out of 303 male subjects and 1 out of 725 female subjects developed persistent proteinuria every year. Subjects with diabetes, hypertension and reduced renal function had a 2 or 3 times higher risk for the incidence of persistent proteinuria in both males and females.     

Relationship between kidney damage and stroke types in Japanese patients

Background

Kidney disease is a known risk factor for stroke. This study investigated the relationship between kidney damage and stroke types.

Methods

A total of 525 incident stroke patients were registered and followed for 1?year. The prevalence of kidney damage [proteinuria and/or renal insufficiency (estimated glomerular filtration rate <60?ml/min/1.73?m²)] in incident stroke and its effects on 1-year prognosis were examined.

Results

Among all stroke patients, kidney damage and its component (proteinuria and renal insufficiency) were commonly observed (48.2, 25.5, and 33.9%, respectively). The prevalence of ischemic stroke was significantly higher in patients with kidney damage (75.9%) than in those without (58.9%). The most frequent type of stroke among all patients with kidney damage and renal insufficiency only was cardioembolic infarction. In contrast, in patients with proteinuria only and patients without kidney damage, the most frequent type was subcortical and subarachnoid hemorrhage, respectively. Multiple logistic regression analysis showed that kidney damage or the combination of its components were independently associated with 1-year death [odds ratio (OR) 3.04, 95% confidence interval (CI) 1.40–6.59, P?=?0.005 for kidney damage, OR 2.82, 95% CI 1.05–7.58, P?=?0.040 for proteinuria only, and OR 5.77, 95% CI 2.23–15.0, P?Conclusions This study shows that kidney damage is common in Japanese stroke patients, and proteinuria and renal insufficiency are differentially related to development and prognosis, depending stroke types.     

Trends and variations in utilization of nephron-sparing procedures for stage I kidney cancer in the United States

Purpose

The incidental detection of early-stage kidney tumors is increasing in the United States. Nephron-sparing approaches (NS) to managing these tumors are equivalent to radical nephrectomy (RN) in oncologic outcomes and have a decreased impact on renal function. Our objective was to evaluate trends in the use of NS over the past decade and the socioeconomic factors associated with its use.

Methods

The National Cancer Database was queried to identify patients with stage I kidney cancer between 2000 and 2008. Patients were classified by the type of surgery as NS (local destruction and local excision) or RN. Patients were further categorized by age, race, insurance status, and income. Log-binomial regression was used to estimate prevalence ratios (PR) for the proportion of NS to RN according to demographic and socioeconomic characteristics.

Results

From 2000 to 2008, there were 142,194 cases of kidney cancer reported to the NCDB. In these cases, 43,034 (30.3 %) patients had NS, and 86,431 (60.78 %) patients had RN. The prevalence of NS increased 10 % per year (PR = 1.10, p < 0.0001)—from 20.0 % in 2000 to 45.1 % in 2008. Older age, lower income, Black race, Hispanic ethnicity, and lack of health insurance were associated with a decreased prevalence of NS.

Conclusions

NS as a treatment for stage I kidney cancer has increased steadily since 2000. Age, racial, and socioeconomic differences may exist in the utilization of NS. Additional analyses, with patient level data, are required to address the independent significance of these variables in an effort to develop strategies to mitigate these potential disparities.     

Factors related to nephrotic-range proteinuria in late-stage chronic kidney disease patients with diabetes mellitus

Purpose

Diabetic nephropathy and proteinuria are important risk factors for both end-stage renal disease and cardiovascular events. The present study aimed to identify the factors associated with nephrotic-range proteinuria in patients with advanced diabetic nephropathy.

Methods

This cross-sectional study enrolled 386 diabetic patients with chronic kidney disease (CKD) stages 3–5, from our outpatient Department of Nephrology. Urinary protein-to-creatinine ratio was recorded. Additionally, other laboratory parameters, body mass index, blood pressure, comorbidities, and medications were also reviewed.

Results

The mean age of the patients was 65.1 ± 11.6 years. Among patients with CKD stage 3 and 4, the odds ratio (OR) for nephrotic-range proteinuria in relation with systolic blood pressure significantly increased starting from 121 mmHg (OR 7.04 and 11.79 for systolic blood pressure of 121–140 and ≥141 mmHg, respectively, in comparison with systolic blood pressure below 121 mmHg). In addition, serum phosphorus ≥4.7 mg/dl was associated with significantly higher risk (OR 15.45) for severe proteinuria, compared with a phosphorus level ≤2.6 mg/dl. Finally, hypertriglyceridemia ≥241 mg/dl was also associated with higher OR for severe proteinuria, compared with a triglyceride level ≤200 mg/dl. Similar associations were found in patients with CKD stage 5.

Conclusions

Higher systolic blood pressure, serum phosphorus, and triglyceride levels are associated with nephrotic-range proteinuria in patients with diabetic nephropathy and CKD stage 3–5. Further studies should clarify whether a reduction in serum phosphorus would lead to a decrease in proteinuria in these patients.     

A nationwide study of mass urine screening tests on Korean school children and implications for chronic kidney disease management

Background

Since 1998, urine screening tests have been performed on school children in Korea. We report the findings of the screening program that analyzed patients with proteinuria and/or hematuria.

Methods

Between 1999 and 2008, 5,114 children were referred to pediatric nephrologists at seven nationwide hospitals. Renal biopsies were performed on 1,478 children [28.79 % of total subjects; 26.77 % for isolated hematuria (IH), 9.09 % for isolated proteinuria (IP), and 51.19 % for combined hematuria and proteinuria (CHP)] who showed abnormal renal function, persistent hematuria and/or proteinuria for more than 6 months, nephrotic-range proteinuria, or those with underlying systemic diseases.

Results

Chronic glomerulonephritis (GN) was detected in 25 % of all visiting subjects. The most common findings in renal biopsies were immunoglobulin A (IgA) nephropathy in 38.97 %, mesangial proliferative GN in 24.29 %, and thin basement membrane nephropathy in 13.13 %. Compared with the relative frequency of renal diseases associated with urinary abnormalities, CHP (46.90 %) and nephrotic-range proteinuria (69.96 %) groups had more frequent GN than the others. Abnormal findings on renal ultrasound with or without Doppler scan were noted in 462 cases (suspected nutcracker phenomenon, 159; increased parenchymal echogenicity, 92; hydronephrosis, 75; simple cyst, 47).

Conclusion

Mass urine screening tests could detect asymptomatic GN in its early stages. Initial aggressive diagnosis and treatment for CHP and nephrotic-range groups may prove helpful as interventions that delay chronic kidney disease progression. These findings may assist in the development of diagnostic and management guidelines for relatively mild urinary abnormalities, such as IH or low-grade IP.     

Severity of nephrotic IgA nephropathy according to the Oxford classification

Background

IgA nephropathy with nephrotic syndrome (nephrotic IgAN) is a rare form of IgAN. Its prognosis and response to steroid therapy are still controversial because the differential diagnosis between nephrotic IgAN and minimal change nephrotic syndrome with IgA depositions is sometimes confused.

Methods

In this retrospective cohort analysis, we accurately diagnosed 42 cases of nephrotic IgAN (4.4%) from 954 IgAN patients, according to the Oxford classification. We analyzed the clinical and histological data, prognosis, and response to steroid therapy.

Results

In nephrotic IgAN, mean estimated glomerular filtration rate (eGFR) was 51.1?±?24.6?ml/min, proteinuria was 5.71?±?2.56?g/day, and urinary red blood cells were 51.0?±?37.8 high power field. Both active and chronic histological lesions were observed. Cumulative renal survival rate was significantly lower in nephrotic IgAN than in non-nephrotic IgAN (the control group consisted of 47 non-nephrotic IgAN patients diagnosed between 1995 and 1996) (log-rank test: P?Conclusion Nephrotic IgAN is a very severe form of IgAN, with renal dysfunction, massive hematuria, and active and chronic histopathological lesions. Renal outcome is severe; however, steroid therapy can improve prognosis in cases with higher eGFR and lower T-grade, according to the Oxford classification.     

Prevalence of renal disease within an urban HIV-infected cohort in northern Italy

Background

Renal disease is an increasingly recognized noninfectious comorbidity associated with human immunodeficiency virus (HIV) infection.

Methods

Our retrospective, cross-sectional study evaluated prevalence of nephropathy among HIV-infected patients followed up in our outpatient clinic during the year 2011. Renal dysfunction and chronic kidney disease (CKD) were defined as estimated glomerular filtration rate (eGFR) <90 ml/min per 1.73 m² and as renal damage or eGFR <60 ml/min per 1.73 m² over a 3-month or greater period, respectively.

Results

We enrolled 894 HIV-infected patients with a mean age of 44.2 years and a mean current CD4 lymphocyte count of 508 cells/mm³. The prevalence of renal dysfunction and CKD was 27.4 and 21.3 %, respectively. Older age, male gender, hypertension, diabetes, proteinuria, hypertriglyceridemia, lower nadir CD4 cell count, current use of tenofovir or tenofovir plus a ritonavir-boosted protease inhibitor were independently associated with renal dysfunction.

Conclusion

Renal dysfunction is a frequent comorbidity among HIV-infected persons and requires a careful clinical and laboratory monitoring of renal function.     

A female with X-linked Alport syndrome and compound heterozygous COL4A5 mutations

Background

Female subjects with X-linked Alport syndrome have a single COL4A5 mutation, germ cell mosaicism in affected tissues and typically develop renal failure later or less often than male subjects. Women with two mutations are exceedingly rare, and usually have consanguineous parents or uniparental disomy. We describe here a 20-year-old woman who inherited two different COL4A5 variants, one from her father (c.2677G>C) and one from her mother (c.384 +1 G>A).

Case-diagnosis/treatment

The index case had normal renal function, proteinuria and no clinically detectable hearing loss, or ocular abnormalities. Her father and paternal uncle developed end-stage renal disease at 37 and 28 years respectively, together with hearing loss, but not lenticonus or central retinopathy. Her mother had mildly impaired renal function, proteinuria, hearing loss, but no ocular abnormalities. Her maternal grandfather and 22-year-old brother, both with this mutation, developed renal failure by 28 years with hearing loss, or had proteinuria and hearing loss respectively.

Conclusion

The index case has clinical features consistent with germ cell mosaicism of two COL45A mutations associated with adult-onset renal failure, but no ocular abnormalities. Her risk of renal failure is high, but the rate of progression to end-stage disease depends on the underlying mutations, and disease modification with renin–angiotensin blockade.     

Positive C1q staining associated with poor renal outcome in membranoproliferative glomerulonephritis

Background

Pathogenesis and clinical prognosis of membranoproliferative glomerulonephritis (MPGN) has not yet been established.

Methods

We conducted a retrospective study of 41 patients with MPGN (type I and III) and examined the renal survival. In addition, factors contributing to survival time were analyzed.

Results

Fourteen patients (34 %) were classified into the renal death group. Patients with nephrotic syndrome and positive C1q staining of glomerular deposits showed a particularly poor prognosis. Significantly higher frequency of nephrotic syndrome and higher urinary protein excretion were observed in the renal death group (p = 0.0002, p = 0.0002) than in the renal survival group. The intensity of C1q staining was positively correlated with the severity of the proteinuria (p = 0.004). Factors that influenced the survival time were positive C1q staining of glomerular deposits (p = 0.003), presence of nephrotic syndrome (p = 0.004), serum albumin (p = 0.02), and proteinuria (p = 0.04).

Conclusions

C1q staining in glomerular deposits and nephrotic syndrome were important factors influencing the prognosis and outcome in MPGN patients. C1q deposition may play a key role in the pathogenesis of MPGN, as evidenced by numerous observations, such as induction of proteinuria.