Complement Inhibitors in Rare Diseases / 罕见病研究

The complement system is a self-protection mechanism of the human body. The abnormal activation of the complement system is involved in the occurrence and development of various diseases. The application of complement inhibitors in many rare diseases was a milestone in leading to the progress of such disease as paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and others. Recently, the application of complement inhibitors has gradually expanded to other complement-related diseases. This review summarizes the literature on the current application of complement inhibitors in rare diseases and looks into the prospects of the application in the rare diseases.

Construction and Application of National Rare Diseases Registry System of China / 罕见病研究

Rare diseases have been a major challenge for clinical medicine and public health challenge in China. One of the effective measures is to conduct proactive research on rare diseases to deal with the disease burden of the diseases. However, low prevalence, disperse distribution of patients, lack of knowledge about the disease course, and phenotype heterogeneity hamper the development of research for rare diseases. Recently, it has been found that patients registry is effective in understanding the course of the disease and accu- mulating the cases and data of clinical research or clinical trial design. At present, most of developed countries or regions in the world have promoted clinical research and clinical trials of new medications on rare diseases by using the registration of rare disease. In 2016, Peking Union Medical College Hospital established China's first registry system at the national level-National Rare Disease Registry System of China(NRDRS). NRDRS has accumulated 68 137 cases data registered by the researchers from China's 101 collaborating hospitals in 29 provinces/municipalities/autonomous regions, covering 171 different, and forming 188 cohorts. To date, NRDRS complete the initial stage of resources buildup.Nex stage will be focused on clinical research and clinical trials related to rare diseases based on NRDRS. This article is on the process of building NRDRS, the potential support for conducting clinical research and clinical trials related to rare diseases, and the challenges will be faced.

Anuria, Sudden Blindless, Confusion: A Case of Unusual "Adult Still Disease" / 罕见病研究

A young female patient presented with fever, arthralgia, and rash was diagnosed with adults still's disease. When treated with glucocorticoid steroid, the above patient progressed to anuria, sudden, and confusion. After a teamwork involving different departments, the patient was finally diagnosed with atypical hemolytic uremic syndrome (aHUS) and treated with good outcome. aHUS is a rare disease, while Eculizumab is an orphan drug. The diagnosis and treatment of the patient reveals the importance of multidisciplinary team on the diagnosis and treatment of rare and difficult diseases.

Kimura disease with renal impairment: case series and literature review / 中华肾脏病杂志

Objective:To analyze the clinical and pathological characteristics, treatment and prognosis of renal changes in patients with Kimura disease and improve the clinicians′ understanding on renal manifestations of Kimura disease.Methods:The clinical data of Kimura disease patients with definite diagnosis and detailed data in Peking Union Medical College Hospital from January 1980 to August 2020 were retrospectively analyzed. The patients were divided into renal impairment group and non-renal impairment group according to whether the kidney was involved or not and the related clinical data between the two groups were compared. The patients presenting with nephrotic syndrome were followed up.Results:There were 60 patients with Kimura disease confirmed by pathological diagnosis with 48 males. The median age was 33(3, 62) years old, and the median duration was 36(12, 111) months. There were 18 cases complicated with renal injury in 49 patients with complete routine urine and renal function examination and the main manifestations of renal injury were proteinuria and/or microscopic hematuria. There was no significant difference at age, sex and absolute value of eosinophils between the two groups (all P>0.05). Compared with the renal inpairment group, patients in non-renal inpairment group had longer course of disease, higher levels of hypersensitive C-reactive protein and erythrocyte sedimentation rate, and lower median values of total eosinophils and total IgE, but there was no statistically significant difference (all P>0.05). Among the patients with renal involvement, 6 patients met the diagnostic criteria for nephrotic syndrome, and 5 of them completed renal biopsies. The renal pathological diagnosis was membranous nephropathy in 2 cases and minimal change disease in 3 cases, and no interstitial eosinophil infiltration was found in renal biopsy tissues. These patients had a good response to glucocorticoids and/or immunosuppressive therapy, and achieved complete remission of nephrotic syndrome; at the same time, lymphadenopathy caused by Kimura disease could be well controlled. Conclusions:Kimura disease can combine with various renal lesions, and the pathology of nephrotic syndrome can be membranous nephropathy or minimal change nephropathy. After energetic treatment of glucocorticoids and/or immunosuppressive therapy, nephrotic syndrome can be completely relieved, and lymphadenopathy can be well controlled. The relationship between Kimura disease and renal disease needs further study.

Comparison of cognitive function between patients with hemodialysis and peritoneal dialysis / 中华肾脏病杂志

Objective:To evaluate whether dialysis modality will affect cognitive function in dialysis population.Methods:This was a cross-sectional study. Chronic dialysis patients in our center was screened from July 2013 to July 2014. All of the subjects received brain magnetic resonance imaging (MRI) examination and comprehensive cognitive function evaluation.Results:A total of 189 chronic dialysis patients were enrolled in this study, 122 cases on hemodialysis (HD) and 67 cases on peritoneal dialysis (PD). There was no significant difference in age between HD and PD groups [(56.4±13.2) years vs (56.4±16.1) years, t=0.004, P=0.997]. The dialysis vintage and serum albumin of HD patients was higher than those of PD patients[58.0(16.8, 107.5) months vs 31.0(7.0, 67.0) months, Z=-3.490, P<0.001; (39.6±3.9) g/L vs (35.3±3.8) g/L, t=7.328, P<0.001, respectively]. The prevalence of cerebral small vessel diseases (CSVDs) was comparable between HD and PD groups (all P>0.05). Compared with HD patients, PD patients presented a 11.90-fold risk of immediate memory impairment (95% CI 1.40-101.08, P=0.023) and a 6.18-fold risk of long-delayed memory impairment (95% CI 2.12-18.05, P=0.001). After adjusting for age, educational lever, dialysis vintage, serum creatinine, and CSVDs, the influence of dialysis modality on memory still worked. PD patients presented a 43% risk of executive function impairment of HD patients ( OR=0.43, 95% CI 0.17-1.04, P=0.061). Conclusions:HD patients manifested better memory than PD patients, while PD probably performed better in executive function than HD patients. There was no significant difference in language function between the two groups. The difference in cognitive function may not be related to CSVDs.

Comparison of clinical features in Gitelman syndrome patients with different urinary calcium excretion / 中华肾脏病杂志

Objective:To observe the clinical features in Gitelman syndrome (GS) patients with different urinary calcium excretion, and investigate the value of urinary calcium excretion in the clinical classification for GS.Methods:GS cases from the National Rare Diseases Registry System of China (NRSC) (2016-2018) with SLC12A3 gene screened in Peking Union Medical College Hospital were collected. The features of urinary calcium excretion were analyzed, and the phenotypes of patients with hypocalciuria were compared to those without. Hydrochlorothiazide (HCT) test was performed according to the standard process, and the maximal increment of chloride excretion fraction (ΔFECl) was calculated. Results:A total of 83 GS patients were included, among whom 53 (63.86%) patients had hypocalciuria. The ratio of urinary calcium/creatine was significantly lower in patients with hypocalciuria compared to those without [(0.085±0.058) mmol/mmol vs (0.471±0.284) mmol/mmol, t=7.349, P<0.001]. Age, gender, estimated glomerular filtration rate, blood pressure, serum and urinary electrolytes, and alkalosis were all comparable between groups. Fatigue ( χ2=4.595, P=0.032) and polyuria ( χ2=5.778, P=0.016) were less frequently reported in hypocalciuria patients, while all the other clinical symptoms were comparable. Sixteen patients in each group underwent HCT test, and the median value of ΔFECl was comparable between patients with and without hypocalciuria [0.539%(0.430%, 1.283%) vs 0.829% (0.119%,1.298%), U=130.000, P=0.956], both of which indicated no response to HCT. Conclusions:The proportion of low urinary calcium in GS patients is 63.86%. There is no definite relationship between urinary calcium excretion, phenotype and the extent of NCC dysfunction.

The 473rd case: renal failure, abdominal pain, and mental abnormality / 中华内科杂志

A 43-year-old male presented with elevated serum creatinine for 4 years and developed abdominal pain for 3 days. He started peritoneal dialysis 2 months ago. Dialysis-related peritonitis was ruled out and acute gastroenteritis was diagnosed. The patient was administrated with ertapenem 500 mg/d. An acute mental abnormality developed 3 days later. After excluded organic encephalopathy, ertapenem was discontinued for the suspicion of antibiotic-related encephalopathy. The frequency of peritoneal dialysis was increased to accelerate the clearance of antibiotics. However, the metal abnormality became even more severe. Then a diagnosis of Wernick-Korsakoff syndrome was considered. After the administration of high dose vitamin B 1, the mental disorder dramatically relieved. Vitamin B 1 30 mg/d is maintained during peritoneal dialysis and the mental disorder does not relapse.

The 473rd case: renal failure, abdominal pain, and mental abnormality / 中华内科杂志

A 43-year-old male presented with elevated serum creatinine for 4 years and developed abdominal pain for 3 days. He started peritoneal dialysis 2 months ago. Dialysis-related peritonitis was ruled out and acute gastroenteritis was diagnosed. The patient was administrated with ertapenem 500 mg/d. An acute mental abnormality developed 3 days later. After excluded organic encephalopathy, ertapenem was discontinued for the suspicion of antibiotic-related encephalopathy. The frequency of peritoneal dialysis was increased to accelerate the clearance of antibiotics. However, the metal abnormality became even more severe. Then a diagnosis of Wernick-Korsakoff syndrome was considered. After the administration of high dose vitamin B1, the mental disorder dramatically relieved. Vitamin B1 30 mg/d is maintained during peritoneal dialysis and the mental disorder does not relapse.

Effects of renal Na-Cl co-transporter on calcium homeostasis and bone metabolism / 中华临床营养杂志

Osteoporosis is a global public health problem. The kidney, especially the Na-Cl co-trans-porter ( NCC) located in the renal distal tubular cells, which is an important transporter for urinary calcium reg-ulation, plays an important role in calcium homeostasis and bone metabolism. This review summarized recent re-searches on effects and mechanisms of NCC on calcium and bone metabolism.

Glycemic variability in hemodialysis patients: implications, characteristics and interventions / 中华临床营养杂志

Glycemic variability is an important indicator for glycemic control and an independent risk factor for cardiovascular events and overall mortality in type 2 diabetes.Hemodialysis patients have greater challenge controling glycemic variability because patients of end-stage renal disease generally have more "brittle" glycemic hemostasis and dialysis itself may cause extra disturbance.In this article,we present an overview on the characteristics,cause,potential damage,and intervention of glycemic variability in hemodialysis patients.

Clinicopathological analysis of Sjogren's syndrome complicated with ANCA associated vasculitis with renal involvement / 中华肾脏病杂志

Objective To investigate the clinical and pathological features of patients with a combination of Sjogren's syndrome (SS) and antineutrophil cytoplasmic antibody (ANCA) associated vasculitis with renal involvement.Methods By searching the Peking Union Medical College Hospital medical database and literature between January 1990 and June 2017,patients had a combination of SS and ANCA associated vasculitis with renal involvement were included.Data of clinical information,autoimmune antibodies,renal manifestations and renal pathology were retrieved and analyzed.Results Eighteen patients were enrolled:4 from our hospital and 14 from literature.SS was diagnosed no later than ANCA associated vasculitis in all the patients,among which 83.3％(15/18) of patients had extra-glandular and extra-renal organs involved.All the patients were tested positive for myeloperoxidase (MPO)-ANCA,and only two were protein 3 (PR3)-ANCA positive concurrently.The positivity rates of antinuclear antibody (ANA),rheumatoid factor (RF),anti-SSA antibody,and anti-SSB antibody were 83.3％(15/18),55.6％(10/18),77.8％(14/18),and 38.9％(7/18),respectively.The renal manifestations were characterized by renal insufficiency with a median serum creatinine of 174 μmol/L,hematuria,moderate proteinuria with a median 24 hour urine protein of 1.70 g,and necrotizing vasculitis with oligo-immune complex and varying degrees of interstitial damage in pathology.Conclusions A combination of Sjogren's syndrome and ANCA associated vasculitis with renal involvement is rare in clinical setting,and almost all of the patients are MPO-ANCA positive,with high probability of ANA positivity and extra-glandular involvement.Physicians should beware of ANCA associated glomerulonephritis in SS patients with inexplicable renal dysfunction and renal biopsy should be carried out in time.

Analysis of heterogeneity in kidney function decline in the aged population / 中华老年医学杂志

Objective To study the rate of kidney function decline and the influencing factors in the aged population. Methods This was a prospective population-based study of 468 participants aged 65 years and older. All participants’ general health information and serum creatinine levels were collected as the baseline. After a 3-year follow-up ,the serum creatinine level of each participant was measured again.Kidney function was assessed with estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease-Epidemiology Collaboration ( CKD-EPI ) equation. Outcomes of interest were mean eGFR decline and rapid decline in eGFR (annual eGFR loss≥3 ml·min－1·1.73 m －2).Risk factors were analyzed with Logistic regression. Results At baseline ,the mean age of participants was(78.4 ± 8.7)years and the mean eGFR was(74.8 ± 14.5)ml ·min－1·1.73 m －2.Annual eGFR decline was 1.5 ml·min－1·1.73 m －2,with rapid declines in 149 (32%) participants and stable kidney function in 319 (68%) individuals. The rate of kidney function loss slowed down as the age increased.Baseline eGFR was an independent predictor for rapid kidney function decline. The incidence of rapid kidney function decline in individuals with eGFR ≥ 60 ml· min－1·1.73 m －2was 2.40 times (95% CI :1.16-4.98) higher than that of participants with eGFR＜60 ml·min－1·1.73 m －2after adjustment for confounders. Conclusions Kidney function changes in the community-dwelling elderly in China are heterogeneous. Most elderly individuals do not show appreciable kidney function decline over a 3-year period.

Effect of peritoneal dialysis on glycemic variability in patients with diabetes and its clinical implications / 中华临床营养杂志

Objective To compare glycemic profile between diabetic patients receiving peritoneal dialysis and diabetic patients with normal kidney function, and to investigate the impact of peritoneal dialysis on glycemic control through continuous glucose monitor system ( CGMS). Methods 19 diabetic patients with end-stage renal disease receiving regular peritoneal dialysis (DMPD group) and 8 patients with non-diabetic ne-phropathy receiving regular peritoneal dialysis ( PD group) were randomly selected and matched with 20 diabetic patients with normal kidney function (DM group) based on age, gender and 72 hours mean glucose. CGMS were applied on all patients for 72 hours. Glycemic variability parameters were compared among the three groups. Results Peritoneal transport function was positively correlated with mean glucose, glucose standard deviation and mean amplitude of glycemic excursion. Compared with PD group, multiple variation parameters, such as intraday glycemic standard deviation (P<0. 001), covariant efficiency (P=0. 009) and mean of daily difference (P=0. 043), were significantly lower in DMPD group. Though both DMPD and DM group exhibited profile as trough in wee hours and post-prandial hyperglycemia, DMPD had higher glycemic level in wee hours (P<0. 001). Conclusion Diabetic patients with end-stage renal disease receiving regular peritoneal dialysis have smaller glucose variability than diabetic patients with normal renal function.

A clinical and hereditary analysis of novel complex heterozygous KCNJ1 mutation in a Bartter syndrome type Ⅱ patient / 中华内科杂志

Bartter syndrome (BS) is a hereditary condition transmitted as an autosomal recessive (Bartter type 1 to 4) or dominant trait (Bartter type 5).The disease associates hypokalemic alkalosis with varying degrees of hypercalciuria.Here we presented a case (BS type Ⅱ) of a 17 years old female presented with polyhydramnios,polyuria,nephrocalcinosis and hypokalemia,which was alleviated after treatment with celecoxib and vitamin D3.DNA sequencing identified compound heterozygous KCNJ1 gene mutations,c.931 C ＞ T (p.R311 W) and c.445-446insCCTGAACAC (p.V149Afs,150X),with the latter a novel mutation.Her father and mother were heterozygous carriers of c.931C ＞ T (p.R311W) and c.445-446insCCTGAACAC (p.V149Afs,150X),respectively.In conclusion,this case of BS type 1 is caused by a novel compound heterozygous KCNJ1 mutation.Further studies are needed to verify the effect of celecoxib in BS patients.

Long-term survival analysis of the elderly peritoneal dialysis patients / 中华肾脏病杂志

Objective@#To analyze the clinical data of the elderly peritoneal dialysis (PD) patients in Peking Union Medical College Hospital (PUMCH), and to find the risk factors for the long-term survival.@*Methods@#Baseline data and the outcome of maintenance PD patients from 1996-03 to 2015-09-30 were collected for a retrospective cohort study. Patients were divided into the non-elderly group (<65 years old), the 65-79 years old group and the ≥80 years old group, and were follow to 2016-09-30. The survival rate was calculated by Kaplan-Meier method and the risk factors of outcome were analyzed by the Cox's regression model.@*Results@#Among 577 PD patients, about 243(42.1%) were elderly patients, including 207 patients aged between 65 and 79 years (35.9%) and 36 patients aged 80 or more (6.2%). The most common primary disease causing PD was diabetic nephropathy (DN) for both elderly and non-elderly patients. The 1-year, 3-year, 5-year survival rate of patients aged between 65 and 79 years were 87.0%, 61.9%, 32.4% respectively, and 72.5%, 48.5%, 27.3% for the ≥80 years old group. The dominating reasons of death were cardiovascular events and infection. There was no difference of technical survival rates among three groups, and the most common reason for technical failure was peritonitis. For elderly patients, diabetes (HR=2.193, 95% CI 1.445-3.328, P<0.001) and lower baseline serum albumin (HR=0.968, 95%CI 0.940-0.996, P=0.026) were independent risk factors for death. However, for non-elderly patients, diabetes (HR=3.746, 95%CI 2.149-6.529, P<0.001) was the only independent risk factor for death.@*Conclusions@#Cardiovascular diseases and infection are the main reasons for death among the elderly PD patients in PUMCH. Diabetes and lower baseline serum albumin may predict the mortality of elderly PD patients independently. Better management of nutrition might improve survival in elderly PD patients.

Adonesine A1 receptor and megalin defect in diabetic mice with early kidney disease / 中华肾脏病杂志

Objective To observe the effect of adenosine A1 receptor (A1AR) on the megalin defect in type 1 diabetic mice with early kidney disease.Methods 7-8 week-old,baseline body weight and fasting blood glucose matched wild type (WT) C57BL/6J mice were selected,and randomly divided into two groups:control group (n=6) and WT DM group (n=6).In the same way,male A1AR knock-out C57BL/6J mice were selected as A1AR-/-DM group (n=6).DM model was established by intraperitoneal injection of streptozocin.The blood glucose (BG),body weight (BW),kidney weight (KW),24 h proteinuria (24hUP) and albumin creatine ratio (ACR) were measured at 4 weeks.The renal pathological lesion was observed and the expression of megalin in proximal tubules was examined by immunohistochemistry.The expression of caspase-1,IL-18 and A1AR were detected by Western blotting.Results At 4th week,compared with WT control mice,the BG,BW,KW and 24hUP of WT DM mice were increased significantly (n=6,P ＜ 0.01),with the pathological glomerular enlargement,mesangial cell proliferation,extracellular matrix accumulation and renal tubule hypertrophy being observed.Immunohistochemistry revealed decreased expression of megalin,an important multiligand protein receptor on the brush border of proximal tubular epithelial cells in WT DM mice,which was correlated with 24hUP (r=-0.645,P ＜ 0.01).Compared with the control mice,the expressions of caspase-1,IL-18 and A1AR were significantly increased in WT DM mice (P ＜ 0.05).For A1AR-/-DM mice,more serious pathological lesion and megalin defect,together with increasing of casapase-1 and heavier proteinuria were observed than those in WT DM mice.Conclusion A1AR may play a protective role in megalin expression of diabetic mice with early kidney disease,in which the mechanism may be associated with caspase-1 related pyroptosis pathway.The details need further exploration.

Characteristics and risk factors of lethal peritoneal dialysis related peritonitis / 基础医学与临床

Objective To analyze the characteristics of lethal peritoneal dialysis related peritonitis and to define the risk factors.Methods All patients who developed PD related peritonitis between Jan.1999 and May 2015 in PUMCH were included.Clinical profiles were collected.Patients were divided into mortality group(n=16) and non-mortality group(n=182) according to whether peritonitis causing mortality.Baseline clinical profiles were compared between two groups.Cox regression analysis was used to define the risk factors for mortality.Results White blood cells [(10.2±6.3)×109/L vs (5.8±1.8)×109/L,P<0.05] increased,but serum albumin[(25.2±8.5)g/L vs (34.0±6.3)g/L,P<0.05] and potassium concentration [(3.5±0.9)mmol/L vs (4.5±1.0)mmol/L,P<0.05] decreased at the time of lethal peritonitis bacteria and fungus cultures were positive in half of the patients as bacteria (31.2%),fungus (12.5%)and mycobacterium tuberculosis (6.25%).Multiple cox regression analysis identified cardiovascular disease as the independent risk factor for peritonitis related mortality (HR 9.318,95% CI 1.875~46.305,P<0.01).Conclusions Peritonitis of patients with cardiovascular disease may cause death.

Efficiency of glucocorticoid treatment in IgA nephropathy with massive proteinuria / 中华肾脏病杂志

Objective To investigate the clinicopathological characteristics of IgAN patients with massive proteinuria,as well as their treatment response to glucocorticoids and long-term prognosis.Methods Clinical and pathological parameters were collected in patients diagnosed with IgA nephropathy in our hospital from Jan 2003 to Oct 2015.Patients were followed up for at least six months under the treatment with full dosage of glucocorticoids.Responses of patients with and without nephrotic syndrome were compared.Results A total of 156 patients were enrolled for the analysis (86 patients in the nephropathic proteinuria group,and 70 patients in the nephrotic syndrome group).Patients presented with nephrotic syndrome showed higher proportion of IgM deposition in renal slides.There exited no difference in treatment response to glucocorticoids between the two groups.Patients with full or partial remission showed a better prognosis by Kaplan-Meier analysis than no remission group (P ＜ 0.001).The ratio of segmental sclerosis was negatively correlated with treatment response to glucocorticoids by multiple linear regression (3 value=-0.330,P ＜ 0.001).Multivariate Cox regression model showed that glomerular density (HR=0.45,P=0.02) and eGFR (HR=0.95,P=0.001)were independent influential factors for renal survival.Conclusions Patients presented with nephrotic syndrome show higher proportion of IgM deposition in renal slides.Patients in remission after treatment with 6-month glucocorticoids present a better prognosis than no remission patients,and glomerular density as well as eGFR are independent influential factors for renal survival.

Validation of the new histopathological classification of ANCA associated glomerulonephritis and its correlation with renal outcome / 中华肾脏病杂志

Objective To assess the predictive value of Berden classification in ANCA associated glomerulonephritis.Methods Patients with confirmed ANCA associated glomerulonephritis were included,by retrieving the medical database in Peking Union Medical College Hospital from January 2000 to May 2015.Their detailed information during hospitalization and follow-up was recorded.The patients were divided into four categories based on Berden classification.The differences in clinical characters,renal function and response for treatment were compared.Results Among the 88 patients with ANCA-associated glomerulonephritis,19 (21.6％),21 (23.9％),32 (36.4％)and 16 (18.2％) patients were classified as focal,mixed,crescentic and sclerotic category.22 patients developed ESRD,and 19 patients died during follow up (1 patient developed ESRD before died).The mean estimated glomerular filtration rate (eGFR) at baseline was 68.04,25.45,30.04,15.16 ml·min-1·(1.73 m2)-1 (P ＜ 0.05) in focal,crescentic,mixed and sclerotic category,respectively.During follow-up period,focal category always had the best renal function,while sclerotic category had the worst renal function.Crescentic category and mixed category were similar and in the middle.Remission rate at 6m was 62.5％,73.7％,57.5％,30.8％(P ＞ 0.05).And crescentic category had the greatest improvement in eGFR at 6m.Conclusions Focal category had relatively preserved renal function and favorable renal outcome,while the sclerotic category had the worst renal outcome.Crescentic and mixed category had an intermediate outcome.We support the use of the Berden classification in predicting the renal prognosis of patients with ANCA associated glomerulonephritis.

Clinical and pathological analysis of patients presenting renal lesion and monoclonal gammopathy / 中华肾脏病杂志

Objectives To analyze the spectrum of renal diseases associated with monoclonal gammopathy and unrelated renal diseases.Methods Hospitalized patients in Peking Union Medical College Hospital who underwent renal biopsy between January,2013 and December,2015.They had monoclonal gammopathy on serum protein electrophoresis (SPE),serum immunofixation electrophoresis (IFE),urine IFE and/or serum free light chain (FLC).64 patients met the inclusion criteria and were classified as monoclonal gammopathy of renal significance (MGRS) (n=36),monoclonal gammopathy of undetermined significance (MGUS) (n=17) and hematologic malignancy (n=11).Results Renal lesions in MGRS subgroup included light chain amyloidosis (n=28,77.8％),light chain deposition disease (n=7,19.4％),and fibrillary glomerulopathy (n=l,2.8％).eGFR in light chain amyloidosis subgroup differed significantly,compared with light chain deposition disease [eGFR 93 ml· min-1 · (1.73m2)-1 vs 28 ml· min-1 · (1.73 m2) 1,P ＜ 0.01],as well as HTN incidence (35.7％ vs 100.0％,P ＜ 0.01).Renal diseases in MGUS subgroup included membranous nephropathy (n=10,58.8％),focal segmental glomerulosclerosis (n=3,17.6％),diabetic glomerulopathy (n=l,5.9％),Henoch-Schonlein purpura nephritis (n=l,5.9％),anti-glomerular basement membrane disease concurrent with membranous nephropathy (n=l,5.9％) and glomerulomegaly (n=l,5.9％).Various renal lesions related/unrelated to hematologic malignancy were seen in third subgroup,including light chain cast nephropathy (n=3,27.3％),tubulo-interstitial lesions (n=2,18.2％),light chain amyloidosis (n=1,9.1％),light chain deposition disease(n=1,9.1％),IgA nephropathy (n=1,9.1％),mesangial proliferative glomerulonephritis (n=l,9.1％),endocapillary proliferative glomerulonephritis (n=1,9.1％) and acute tubular necrosis (n=1,9.1％).Positive rates of SPE,serun IFE and urine IFE in MGRS subgroup were 40.6％,52.8％ and 69.4％,respectively.Positive rates of SPE,serum IFE and urine IFE in MGUS subgroup were 68.8％,100.0％ and 37.5％,respectively.Positive rates of SPE,serum IFE and urine IFE in hematologic malignancy subgroup were 54.5％,72.7％ and 81.8％ respectively.MGRS and MGUS subgroups differed significantly in positive rate of serum IFE (P ＜ 0.001).Abnormal rates of serum FLC ratio in above three subgroups were 83.3％,17.6％ and 90.9％,respectively,with that in MGUS group being significantly lower than the rates in other two groups (P ＜ 0.001,respectively).Conclusions The significance of monoclonal gammopathy in patients with renal disease should be evaluated by other clinical data,as well as renal pathology.