Systemic Immunomodulatory Effects of Combinatorial Treatment of Thalidomide and Dexamethasone on T Cells and Other Immune Cells

Purpose@#In organ transplantation, the need for immune modulation rather than immune suppression has been emphasized. In this study, we investigated whether combinatorial treatments of with thalidomide (TM) and dexamethasone (DX) might be new approaches to induce systemic immunomodulation on T cells and other immune cells that regulate the expression of co-inhibitory molecules. @*Materials and Methods@#Naïve splenic T cells from C57BL/6 mice were sort-purified and cultured in vitro for CD4+ T cell proliferation and regulatory T cell (Treg) conversion in the presence of TM or/and DX. Expression of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) in proliferated and converted T cells was quantified by flow cytometry. We also quantified in vivo expression of CTLA-4 and PD-1 on splenic CD4+ T cells and other immune cells isolated from TM- or/and DX-treated mice. Mixed lymphocytes reactions (MLR) were performed to evaluate the capacity of immune cells in carrying out immune responses. @*Results@#CTLA-4 expressions in effector T cells in vivo and in Tregs in vivo/vitro significantly increased upon TM/DX combinatorial treatment. Corresponding to increased CTLA-4 expression in T cells, the expression of ligand molecules for CTLA-4 significantly increased in splenic dendritic cells in TM/DX-treated groups. In addition, MLR results demonstrated that splenocytes isolated from TM/DX-treated mice significantly suppressed the proliferation of T cells isolated from other strains. @*Conclusion@#Based on these results, we suggest that TM/DX combinatorial treatments might be efficient immunomodulatory methods for regulating T cell immunity.

Physicians' perceptions of asymptomatic hyperuricemia in patients with chronic kidney disease: A questionnaire survey

BACKGROUND: Hyperuricemia is associated with the development and progression of chronic kidney disease (CKD) as well as cardiovascular diseases. However, there is no consistent recommendation regarding the treatment of asymptomatic hyperuricemia (AHU) in CKD patients. Here, we surveyed Korean physicians’ perceptions regarding the diagnosis and management of AHU in CKD patients. METHODS: Questionnaires on the management of AHU in CKD patients were emailed to regular members registered with the Korean Society of Nephrology. RESULTS: A total of 158 members answered the questionnaire. Among the respondents, 49.4%/41.1% were considered hyperuricemic in male CKD patients whereas 36.7%/20.9% were considered hyperuricemic in female CKD patients when defined by serum uric acid level over 7.0/8.0 mg/dL, respectively. A total of 80.4% reported treating AHU in CKD patients. The most important reasons to treat AHU in CKD patients were renal function preservation followed by cerebro-cardiac protection. Majority of respondents (59.5%) thought that uric acid-lowering agents (ULAs) were the most effective method for controlling serum uric acid levels. Approximately 80% chose febuxostat as the preferred medication. A total of 32.3% and 31.0%, respectively, initiated ULA treatment if the serum uric acid level was more than 8.0 or 9.0 mg/dL, respectively. In addition, 39.2% and 30.4% answered that target serum uric acid levels of less than 6.0 or 7.0 mg/dL, respectively, were appropriate. The two major hurdles to prescribing ULAs were concerns of adverse reactions and the existing lack of evidence (i.e., the absence of Korean guidelines). CONCLUSION: Most Korean physicians treat AHU in CKD patients to prevent CKD progression and cerebro-cardiovascular complications.

Safety and Efficacy of Tolvaptan in Korean Patients with Hyponatremia Caused by the Syndrome of Inappropriate Antidiuretic Hormone

BACKGROUND: The aim of this multicenter study was to evaluate the safety and efficacy of tolvaptan (TLV) in Korean patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). METHODS: Of 51 enrolled patients with SIADH, 39 patients (16 female patients, aged 70.8 ± 11.3 years) were included in an intention to treat analysis. All patients received 15 mg/day as the initial dose, and the dose was then increased up to 60 mg/day (as needed) until day 4. RESULTS: Serum sodium increased significantly from baseline during the first 24 hours (126.8 ± 4.3 vs. 133.7 ± 3.8 mmol/L, P < 0.001), rose gradually between days 1 and 4 (133.7 ± 3.8 vs. 135.6 ± 3.6 mmol/L, P < 0.05), and then plateaued until day 11 (136.7 ± 4.5 mmol/L). The correlation between the change in serum sodium for the first 24 hours and initial serum sodium concentration was significant (r = −0.602, P < 0.001). In severe hyponatremia (< 125 mmol/L), the change was significantly higher (11.1 ± 4.8 mmol/L) than in moderate (6.4 ± 2.5 mmol/L, P < 0.05) or mild hyponatremia (4.3 ± 3.3 mmol/L, P < 0.01). In addition, logistic regression analysis showed that body weight (odds ratio [OR], 0.858; 95% confidence interval [CI], 0.775–0.976; P = 0.020) and body mass index (BMI) (OR, 0.692; 95% CI, 0.500–0.956; P = 0.026) were associated with rapid correction. No serious adverse events were reported, but in 13% of patients hyponatremia was overcorrected. CONCLUSION: TLV is effective in correcting hyponatremia and well-tolerated in Korean patients with SIADH. However, those with low body weight, low BMI or severe hyponatremia, could be vulnerable to overcorrection with the initial dose of 15 mg TLV.

Association of Serotonin 1A Receptor Polymorphism with Variation in Health-Related Quality of Life in Korean Hemodialysis Patients

OBJECTIVE: Hemodialysis patients may have psychological distress and reduced quality of life (QoL) related to chronic physical health problems. Genetic polymorphisms associated with reduced QoL in hemodialysis patients. The aim of this study was to investigate the relationship between genetic polymorphisms and variation in health-related QoL in Korean hemodialysis patients. METHODS: The 36-item Short-Form Health Survey and the Korean Hospital Anxiety and Depression Scale were used to assess health-related QoL and psychological distress, respectively. Twenty hundred and five clinically stable patients from 6 hemodialysis centers have participated with informed consents. Sociodemographic factors, clinical factors, and genotypes of serotonin 1A receptor, brain-derived neurotrophic factors, and glucocorticoid receptor were assessed. Independent t-tests, correlation analyses, multiple regression analyses were performed for statistical analyses. RESULTS: The serotonin 1A receptor CC genotype group showed significantly higher physical and mental QoL levels than those with the GG/GC genotypes. In the final linear regression analysis, serotonin 1A receptor CC genotype was significantly associated with positive physical and mental QoL levels. CONCLUSION: ConclusionaaSerotonin 1A receptor polymorphism, as well as age and depression, were significantly associated with mental and physical QoL in hemodialysis patients. Functional activity in the serotonin receptor system may have a modulating effect on health-related QoL in hemodialysis patients.

Effect of Personalized Nutritional Counseling on the Nutritional Status of Hemodialysis Patients

This study set out to evaluate the impact of personalized nutritional counseling (PNC) on the nutritional status of hemodialysis (HD) patients. This was an intervention study for 10 months at 2 hospitals. Anthropometric, biochemical, dietary, and body composition parameters were measured at baseline and after 3 and 6 months of PNC. A total of 42 patients (23 men and 19 women) were included. Intake of dietary protein, serum albumin, and cholesterol levels had increased significantly from baseline to month 6 (p < 0.05). Among the bioelectrical impedance analysis (BIA) parameters, both the body cell mass (BCM) and the fat free mass (FFM) had significantly reduced at month 3 compared to baseline (p < 0.05). However, there was no difference between baseline and month 6. We assessed the nutritional status of the subjects using the malnutrition inflammation score (MIS), and divided them into an adequately nourished (AN) and a malnourished (MN) group at baseline. In the subgroup analysis, serum levels of albumin and cholesterol had increased significantly, particularly from baseline to month 6 in the MN group (p < 0.05). This study suggests that consecutive PNC contributed to the improvement of the protein intake, serum levels of albumin, cholesterol and to the delay of muscle wasting, which could also have a positive impact on the nutritional status, particularly in malnourished patients receiving HD treatment.

Effect of low-dose valsartan on proteinuria in normotensive immunoglobulin A nephropathy with minimal proteinuria: a randomized trial

BACKGROUND/AIMS: Immunoglobulin A nephropathy (IgAN) is a generally progressive disease, even in patients with favorable prognostic features. In this study, we aimed to investigate the antiproteinuric effect and tolerability of low-dose valsartan (an angiotensin II receptor blocker) therapy in normotensive IgAN patients with minimal proteinuria of less than 0.5 to 1.0 g/day. METHODS: Normotensive IgAN patients, who had persistent proteinuria with a spot urine protein-to-creatinine ratio of 0.3 to 1.0 mg/mg creatinine, were recruited from five hospitals and randomly assigned to either 40 mg of valsartan as the low-dose group or 80 mg of valsartan as the regular-dose group. Clinical and laboratory data were collected at baseline, and at 4, 8, 12, and 24 weeks after valsartan therapy. RESULTS: Forty-three patients (low-dose group, n = 23; regular-dose group, n = 20) were enrolled in the study. Proteinuria decreased significantly not only in the regular-dose group but also in the low-dose group. The change in urine protein-to-creatinine ratio at week 24 was -41.3% +/- 26.1% (p < 0.001) in the regular-dose group and -21.1% +/- 45.1% (p = 0.005) in the low-dose group. In the low-dose group, blood pressure was constant throughout the study period, and there was no symptomatic hypotension. In the regular-dose group, blood pressure decreased at weeks 8 and 12. No significant change in glomerular filtration rate, serum creatinine level, or serum potassium level was observed during the study period. CONCLUSIONS: Our results suggest that low-dose valsartan can significantly reduce proteinuria without causing any intolerability in normotensive IgAN patients with minimal proteinuria.

High Water Intake and Progression of Chronic Kidney Diseases

Impact of water intake on the courses of chronic kidney and urinary tract diseases, such as urolithiasis, urinary tract infections, chronic kidney diseases (CKD), autosomal dominant polycystic kidney diseases and bladder cancer, has recently been studied. It still remains controversial whether increased water intake slows the progression of CKD or not. However, high water intake suppresses plasma levels of arginine vasopressin (AVP), which is expected to be beneficial for the preservation of the kidney function. Previous studies suggest that water intake suppresses plasma levels of AVP, and high levels of AVP have been suggested to play deleterious roles in animal models of kidney disease. Moreover, recent epidemic of CKD of unknown origin, which was supposed to be related to the insufficient water intake and chronic volume depletion, has been reported in Central America, further suggesting that the suppression of AVP by sustained water intake might be beneficial in this CKD population. Indeed, the data from recent studies were consistent with the view that high water intake is associated with slower progression of CKD. However, contradictory findings also exist. The intriguing effects of increased urine volume in preserving the glomerular filtration rate in human patients with CKD require more large and well-designed randomized prospective clinical trials.

Salt Sensitivity and Hypertension: A Paradigm Shift from Kidney Malfunction to Vascular Endothelial Dysfunction

Hypertension is a complex trait determined by both genetic and environmental factors and is a major public health problem due to its high prevalence and concomitant increase in the risk for cardiovascular disease. With the recent large increase of dietary salt intake in most developed countries, the prevalence of hypertension increases tremendously which is about 30% of the world population. There is substantial evidence that suggests some people can effectively excrete high dietary salt intake without an increase in arterial BP, and another people cannot excrete effectively without an increase in arterial BP. Salt sensitivity of BP refers to the BP responses for changes in dietary salt intake to produce meaningful BP increases or decreases. The underlying mechanisms that promote salt sensitivity are complex and range from genetic to environmental influences. The phenotype of salt sensitivity is therefore heterogeneous with multiple mechanisms that potentially link high salt intake to increases in blood pressure. Moreover, excess salt intake has functional and pathological effects on the vasculature that are independent of blood pressure. Epidemiologic data demonstrate the role of high dietary salt intake in mediating cardiovascular and renal morbidity and mortality. Almost five decades ago, Guyton and Coleman proposed that whenever arterial pressure is elevated, pressure natriuresis enhances the excretion of sodium and water until blood volume is reduced sufficiently to return arterial pressure to control values. According to this hypothesis, hypertension can develop only when something impairs the excretory ability of sodium in the kidney. However, recent studies suggest that nonosmotic salt accumulation in the skin interstitium and the endothelial dysfunction which might be caused by the deterioration of vascular endothelial glycocalyx layer (EGL) and the epithelial sodium channel on the endothelial luminal surface (EnNaC) also play an important role in nonosmotic storage of salt. These new concepts emphasize that sodium homeostasis and salt sensitivity seem to be related not only to the kidney malfunction but also to the endothelial dysfunction. Further investigations will be needed to assess the extent to which changes in the sodium buffering capacity of the skin interstitium and develop the treatment strategy for modulating the endothelial dysfunction.

How do We Manage Coronary Artery Disease in Patients with CKD and ESRD?

Chronic kidney disease (CKD) has been shown to be an independent risk factor for cardiovascular events. In addition, patients with pre-dialysis CKD appear to be more likely to die of heart disease than of kidney disease. CKD accelerates coronary artery atherosclerosis by several mechanisms, notably hypertension and dyslipidemia, both of which are known risk factors for coronary artery disease. In addition, CKD alters calcium and phosphorus homeostasis, resulting in hypercalcemia and vascular calcification, including the coronary arteries. Mortality of patients on long-term dialysis therapy is high, with age-adjusted mortality rates of about 25% annually. Because the majority of deaths are caused by cardiovascular disease, routine cardiac catheterization of new dialysis patients was proposed as a means of improving the identification and treatment of high-risk patients. However, clinicians may be uncomfortable exposing asymptomatic patients to such invasive procedures like cardiac catheterization, thus noninvasive cardiac risk stratification was investigated widely as a more palatable alternative to routine diagnostic catheterization. The effective management of coronary artery disease is of paramount importance in uremic patients. The applicability of diagnostic, preventive, and treatment modalities developed in nonuremic populations to patients with kidney failure cannot necessarily be extrapolated from clinical studies in non-kidney failure populations. Noninvasive diagnostic testing in uremic patients is less accurate than in nonuremic populations. Initial data suggest that dobutamine echocardiography may be the preferred diagnostic method. PCI with stenting is a less favorable alternative to CABG, however, it has a faster recovery time, reduced invasiveness, and no overall mortality difference in nondiabetic and non-CKD patients compared with CABG. CABG is associated with reduced repeat revascularizations, greater relief of angina, and increased long term survival. However, CABG is associated with a higher incidence of post-operative risks. The treatment chosen for each patient should be an individualized decision based upon numerous risk factors. CKD is associated with higher rates of CAD, with 44% of all-cause mortality attributable to cardiac disease and about 20% from acute MI. Optimal treatment including aggressive lifestyle modifications and concomitant medical therapy should be implemented in all patients to maximize benefits from either PCI or CABG. Future prospective randomized controlled trials with newer second or third generation DES and bioabsorbable DES are necessary to determine if PCI may be non-inferior to CABG in the future.

Epidermal Proteinase-Activated Receptor-2 Expression is Increased in End-Stage Renal Disease Patients with Pruritus: A Pilot Study

Uremic pruritus is a common problem in patients with end-stage renal disease (ESRD), but the underlying mechanisms are not yet fully understood. We aimed to investigate the association between severity of uremic pruritus and cutaneous serine protease activity, as well as proteinase-activated receptor-2 (PAR-2) expression. Twelve ESRD patients with pruritus, 4 ESRD patients without pruritus, and 6 healthy controls were enrolled. Skin biopsies were obtained from the abdomen. Protease activity and PAR-2 expression in the epidermis were examined by in situ zymography and confocal laser microscopy, respectively. All ESRD patients presented more pronounced cutaneous protease activity compared with that in healthy controls. The skin samples from the patients with pruritus showed higher protease activity than either nonpruritic ESRD patients or healthy controls. The epidermis in all samples of ESRD patients presented higher immunoreactivity against PAR-2 versus those of healthy controls. In addition, correlation analysis between PAR-2 expression and VAS pruritus scores showed a significant positive correlation. Our data suggests that levels of serine protease and PAR-2 expression could play important roles in the pathogenesis of uremic pruritus.

Asymptomatic renal pseudoaneurysm after percutaneous renal biopsy Volume 32, Issue 2, June 2013, pp. 87-89

No abstract available.

Asymptomatic renal pseudoaneurysm after percutaneous renal biopsy

A 37-year-old man was referred to Division of Nephrology for a new renal cystic lesion that was found on ultrasonography. Four years prior to presentation, a percutaneous renal biopsy had been performed. Computed tomography scan showed a 4.4-cm-sized renal artery pseudoaneurysm in the left kidney. Selective renal angiography revealed a pseudoaneurysm in the left lower pole of the kidney. The renal pseudoaneurysmwas successfully embolized with coil. Follow-up Doppler ultrasonography showed no internal blood flow into the aneurysmal sac. His renal function remained stable after coil embolization.

Potassium Balances in Maintenance Hemodialysis

Potassium is abundant in the ICF compartment in the body and its excretion primarily depends on renal (about 90%), and to a lesser extent (about 10%) on colonic excretion. Total body potassium approximated to 50mmol/kg body weight and 2% of total body potassium is in the ECF compartment and 98% of it in the intracellular compartment.Dyskalemia is a frequent electrolyte imbalance observed among the maintenance hemodialysis patients. In case of hyperkalemia, it is frequently "a silent and a potential life threatening electrolyte imbalance" among patients with ESRD under maintenance hemodialysis. The prevalence of hyperkalemia in maintenance HD patients was reported to be about 8.7-10%. Mortality related to the hyperkalemia has been shown to be about 3.1/1,000 patient-years and about 24% of patients with HD required emergency hemodialysis due to severe hyperkalemia. In contrast to the hyperkalemia, much less attention has been paid to the hypokalemia in hemodialysis patients because of the low prevalence under maintenance hemodialysis patients. Severe hypokalemia in the hemodialysis patients usually was resulted from low potassium intake (malnutrition), chronic diarrhea, mineralocorticoid use, and imprudent use of K-exchange resins. Recently, the numbers of the new patients with advanced chronic kidney disease undergoing maintenance hemodialysis are tremendously increasing worldwide. However, the life expectancy of these patients is still much lower than that of the general population. The causes of excess mortality in these patients seem to various, but dyskalemia is a common cause among the patients with ESRD undergoing hemodialysis.

Sulodexide in IgA nephropathy

No abstract available.

Sulodexide in IgA nephropathy

No abstract available.

Severe Symptomatic Hyponatremia Caused by Low Dose Oral Cyclophosphamide: A Case Report / 대한신장학회지

Cyclophosphamide (CY), an alkylating agent, is frequently used in the treatment of various autoimmune disorders and malignancies. Acute hyponatremia is a well-known side effect of moderate to high dose intravenous CY treatment, but is rare in patients treated with low dose intravenous CY. We report the case of a severe symptomatic hyponatremia in a 68-year-old woman with renal impairment who was treated with oral CY (100 mg/day) for anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (GN). This case demonstrates that even oral CY could be associated with life threatening acute hyponatremia and should be used with caution.

Rhabdomyolysis-Induced Acute Kidney Injury Associated with Posterior Reversible Encephalopathy Syndrome / 대한신장학회지

Posterior reversible encephalopathy syndrome (PRES) is characterized by altered mental status, headache, vomiting, visual loss, seizure and reversible posterior subcortical white matter and cortex edema in brain image studies. It is often associated with malignant hypertension and immunosuppression. We present a 30-year-old male with PRES. He was admitted to our hospital with rhabdomyolysis and acute kidney injury (AKI). During the hospital course, he developed acute malignant hypertension accompanied by visual loss and generalized seizure. Brain MRI demonstrated increased signal intensity with gyral swelling in cerebellar hemisphere, parieto-occipital cortex, and subcortical white matter area. Following aggressive blood pressure control and hemodialysis the patient recovered fully without any neurologic or visual complications. We report a case of PRES associated with AKI due to rhabdomyolysis.

Icodextrin Improves the Serum Potassium Profile with the Enhancement of Nutritional Status in Continuous Ambulatory Peritoneal Dialysis Patients

The impact of glucose-free icodextrin (ID) for overnight dwell as compared to conventional glucose-containing dialysate (GD) on potassium (K+) metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients has not yet been investigated. Serum K+ in a total of 255 stable patients (116 on GD and 139 on ID) on CAPD for more than 6 months and in 139 patients on ID before and after ID use (Pre-ID and Post-ID) were observed along with nutritional markers in a 2-year study period (Jan. 2006 to Dec. 2007). The prevalence of hypokalemia was similar between patients on GD and ID (16.7% vs 17.3%), but was lower on Post-ID than Pre-ID (17.3% vs 20.5%) without statistic significance. The mean serum K+ level was higher on ID than on GD (P<0.05) as well as Post-ID than Pre-ID (P<0.001). In the multivariate analysis, serum K+ levels were positively correlated with serum albumin, and creatinine in all patients (P<0.05), and ID-use in younger patients (age< or =56, P<0.001). Serum albumin, creatinine, total CO2, and body mass index were significantly higher on Post-ID than Pre-ID. Icodextrin dialysate for chronic overnight dwell could increase serum K+ levels and lower the prevalence of hypokalemia compared to conventional glucose-containing dialysate. The improved chronic K+ balance in CAPD patients on icodextrin could be related to enhanced nutritional status rather than its impact on acute intracellular K+ redistribution.

The Effect of Cyclosporine on P-cadherin Expression in Experimental Diabetic Nephropathy and Glucose-Stimulated Podocytes / 대한신장학회잡지

PURPOSE: We investigated whether Cyclosporin A (CsA) had the anti-proteinuric effect in diabetic rats and whether it was associated with the alteration of P-cadherin expression. METHODS: Sprague-Dawley rats were injected with diluent (C, N=16) or streptozotocin intraperitoneally (DM, N=16). Eight rats in each group were treated with 10% ethanol or with 1.5 mg/kg/day of CsA (C+CsA and DM+CsA) for 6 weeks. Immortalized mouse podocytes were cultured in media with 5.6 mM glucose (LG), LG+CsA (10-8 M), LG+TGF-beta1, 30 mM glucose (HG), or HG+CsA. Real time-PCR and Western blot were performed for P-cadherin and TGF-beta1 mRNA and protein expression, respectively, with sieved glomeruli and cell lysates. RESULTS: Urinary albumin excretion was significantly higher in DM compared with C rats, and CsA treatment inhibited the increase in albuminuria in DM rats. Glomerular P-cadherin mRNA and protein expression in DM were decreased compared with C rats, and these decreases were significantly inhibited by CsA. Glomerular TGF-beta1 mRNA and protein expression were higher in DM than C rats, and CsA treatment inhibited the increase in TGF-beta1 expression in DM. P-cadherin mRNA and protein expression in HG and LG+TGF-beta1 podocytes were lower than LG cells, and these HG-induced decrements were restored by CsA. CONCLUSION: CsA treatment reduces urinary albumin excretion in DM rats. P-cadherin expression is decreased under diabetic conditions, which is ameliorated by CsA. In addition, inhibition of the increase in glomerular TGF-beta1 expression under diabetic conditions by CsA seems to restore the P-cadherin expression, resulting in the decrease in albuminuria.

Differences in Pathologic Findings and Gene Expressions of Renal Tissue according to Steroid Responsiveness in Adult-Onset Minimal Change Disease / 대한신장학회잡지

PURPOSE: Compared to children, adult MCD patients tend to have a slower response to steroids, however, little is known about the relationships between pathologic findings or the expression of certain gene and the response to steroid treatment in adult-onset MCD. This study was undertaken to investigate the differences in pathologic findings and the mRNA expression of nephrin and glucocorticoid receptor (GCR) in renal tissue according to steroid responsiveness in adult-onset MCD. METHODS: Twenty-eight adult patients who presented with idiopathic nephrotic syndrome at our institution and fulfilled the criteria for MCD clinically and pathologically were chosen for this study. Based on the response to steroid treatment, patients were divided into two groups: early responders (ER) in whom CR was achieved within 4 weeks of steroid treatment; late responders (LR) in whom CR was achieved after 4 weeks of steroid treatment. RESULTS: Of the 28 patients, ER consisted of 20 patients. Time to CR was significantly shorter in ER compared to LR (16.5+/-0.9 vs. 52.0+/-4.9 days, p<0.01). The proportion of patients with minimal IgM deposition on immunofluorescence was significantly higher in LR compared to ER (75.0% vs. 30.0%, p<0.01). On the other hands, the mRNA expression of GCR, assessed by real time-PCR, was significantly lower in LR than that in ER (p<0.005), whereas nephrin mRNA expression was not different between the two groups. CONCLUSION: The presence of glomerular IgM deposition and the amount of GCR in renal tissue may be useful predictors of steroid responsiveness in adult MCD patients.