Chronic Glomerular Nephropathy Research Articles

Urinary SPP1 has potential as a non-invasive diagnostic marker for focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a type of chronic glomerular nephropathy showing characteristic glomerular sclerosis, diagnosed by kidney biopsy. However, it is difficult and expensive to monitor disease progression with repeated renal biopsy in clinical practice, and thus here we explored the feasibility of urine biomarkers as non-invasive diagnostic tools. We downloaded scRNA-seq datasets of 20 urine cell samples and 3 kidney tissues and obtained two gene lists encoding extracellular proteins for bioinformatic analysis; in addition, we identified key EP-Genes by immunohistochemical staining and performed bulk RNA sequencing with 12 urine samples. We report that urine cells and kidney cells were correlated. A total of 64 EP-Genes were acquired by intersecting genes of distal tubular cluster with extracellular proteins. Function enrichment analysis showed that EP-Genes might be involved in the immune response and extracellular components. Six key EP-Genes were identified and correlated with renal function. IMC showed that key EP-Genes were located mainly in tubules. Cross verification and examination of a urine RNAseq dataset showed that SPP1 had diagnostic potential for FSGS. The presence of urine SPP1 was primarily associated with macrophage infiltration in kidney, and the pathogenesis of FSGS may be related to innate immunity. Urinary cells seemed to be strongly similar to kidney cells. In summary, SPP1 levels reflect renal function and may have potential as a biomarker for non-invasive diagnosis of FSGS.

MO484: Gender Differences in the Incidence of End-Stage of Renal Disease in Okinawa

Abstract BACKGROUND AND AIMS The incidence of chronic kidney disease (CKD) and its progression to end-stage renal disease (ESRD) differ between genders, so it can be surmised that the incidence of ESRD is different between males and females. Acceptance of dialysis therapy may not necessarily be equal to the incidence of ESRD. Factors such as socio-economic conditions of the family, residential area, risk factors and compliance to the treatment of CKD are not equal among gender. We accessed the gender difference in incidence of ESRD and its risk factors in Okinawa, Japan, a major ESRD epidemic area. METHOD The Okinawa Dialysis Study (OKIDS) registry included all chronic dialysis patients treated in Okinawa, Japan, since 1971. We defined the ESRD as those who survived at least one month on scheduled dialysis therapy (hemodialysis and peritoneal dialysis) to exclude acute kidney injury. We analyzed the annual incidence of ESRD by gender for 30 years from 1971 to 2000. The incidence rate of ESRD was calculated as the number of incident dialysis patients divided by the census population of the previous year in each gender and expressed per million population (pmp). The number of dialysis facilities increased from 1 (1971) to 50 (2000). The census population was increased from 939 742 (1971) to 1 318 220 (2000) in Okinawa. RESULTS A total of 5264 patients, 2981 males and 2265 females, have initiated maintenance hemodialysis during the study period. The incidence rate of ESRD increased from 8.9 to 370 pmp in males and from 0 to 227 pmp in females between 1971 and 2000. The growth was fast and consistent throughout the period in males, while in females, the growth has become slower since 1990. After age-standardized, a similar trend was observed, which increased from 41 to 224 pmp in males and from 36 to 154 pmp in females between 1975 and 2000. For males and females, the age-specific incidence rate in the 60–79 year and >80 year groups increased rapidly, and that in the 40–59 year group increased gradually, whereas in the 0–39 year group have been flat. The age-specific rate in the 60–79 year and >80 year groups for males continued to increase throughout the period, while that for females peaked between 1990 and 1995. In the cause-specific incidence rate, the following trends were observed in males and females. The incident rate caused by chronic glomerular nephropathy increased from the 1970s to the 1980s and then leveled off, while that by diabetic nephropathy increased from the 1980s and that by nephrosclerosis increased from the 1990s. The marked growth was seen in the incident rate caused by diabetic nephropathy for both males and females. The rate increased 31 times for males and 12 times for females in the 20 years from 1981 to 2000. The age- and cause-specific incidence rate has risen remarkably among male diabetic nephropathy in >60 years. CONCLUSION In Okinawa, the incidence rate of ESRD has increased significantly in males compared with females, and the gender difference has been widening. It was suggested that the increase in the number of males with diabetic nephropathy over the age of 60 contributed to this widening of the gender difference.

POS-522 EARLY VERSUS LATE DIALYSIS: TIMING AND MORTALITY

Chronic kidney disease remains one of the diseases with a high cardiovascular morbidity andmortality, especially when approaching the end stage. The correct timing of dialysis initiation remains a controversial issue until now. The aim of this study is to compare early and late dialysis andtheir impact on mortality. This is a retrospective study. We collected sociodemographic, clinical and biological data from the medical records of patients who reached the end stage, divided into two groups : early HDP hemodialysis with a glomerular filtration rate (GFR > 7 ml/min) and late HDT hemodialysis (GFR ≤ 7ml/min). Our study included 149 patients of whom 66 were in the HDT group. The mean age was 59.38 yearsand 64.27 years in the HDT and HDP groups respectively. The mean GFR in the HDT and HDP group was 5.4 ml/min and 9.8 ml/min. The percentages of hypertension, diabetes and coronaryi nsufficiency were respectively in HDT and HDP : 41.35%, 36.47%, 41.38% and 58.65%, 63.53%,58.62%. The main etiologies of CKD were : diabetes (26.56% HDT ; 20.73% HDP), chronic interstitial nephropathy (18.75% HDT ; 23.17% HDP), vascular nephropathy (7.8% HDT ; 4.88% HDP), chronic glomerular nephropathy (9.37% HDT ; 12.19% HDP) and indeterminate (37.5% HDT ; 30.49% HDP) Mortality in the HDT group was 34.85% (n=23) and in the HDP group 48.19% (n=40). There was no significant difference in mortality between the 2 groups (p=0.1014). In our study, mortality was slightly higher in HDP group than among HDT group, but was not significant, which requires larger studies spread over time to confirm or disprove this result.

POS-538 KIDNEY DISEASE IN MULTIPLE MYELOMA

Multiple myeloma (MM) is characterized by a proliferation of malignant plasma cells and a subsequent overabundance of monoclonal paraprotein invading the hematopoietic marrow and other organs such as bone.Kidney disease is a common complication of MM. It can be indicative of the disease, or appear during its course. The objective of our work was to determine the incidence and clinical-biological aspects of renal involvement in multiple myeloma It was a retrospective and descriptive study including patients hospitalized in nephrology department of Sahloul Hospital in Sousse with multiple myeloma and renal disease, during the period from December 2007 to June 2019. We collected 53 patients with an average incidence of 4.8 new cases / year. The average age of our patients was 63.53 years +/- 11.49 years with extremes ranging from 41 years to 85 years. There was a slight male predominance with a sex ratio M / F = 1.2. In more than 50% of cases, MM was hitherto unrecognized and the diagnosis was made during the exploration of renal failure in nephrology department. Only 24.5% of patients were already diagnosed and treated for MM in hematology department and renal failure had occurred during the course of the disease. The circumstances of discovery of renal disease were represented by bone pain and odematous syndrome with urine dipstick proteinuria. General manifestations were dominated by the presence of general deterioration in 35 patients (67.3%) followed by signs of extracellular dehydration which was objectified in 23 patients (34.4%). Acute renal injury (ARI) was found in 43 patients (81.1%). This acute renal failure was secondary to myelomatous tubulopathy in 79.1% of cases; functional in 7% of cases. A functional ARI associated with myelomatous tubulopathy was found in 14% of cases. Myelomatous tubulopathy confirmed by renal puncture biopsy (RPB) in 11 cases. AL amyloidosis was found in 10 cases (18.9%) of which 7 cases were confirmed by RPB and in 3 cases the diagnosis was established by accessory salivary gland biopsy. Histologically unproven chronic glomerular nephropathy was found in 2 cases. Myelomatous tubulopathy is by far the most common renal complications of myeloma and a major cause of acute renal injury, hence the value of screening for renal involvement in any patient followed for myeloma.

POS-710 KIDNEY TRANSPLANT RECIPIENTS WITH A PRETRANSPLANTATION CANCER HISTORY

Pretransplant malignancy (PTM) in remission has long been considered a relative contraindication for organ transplantation due to the heightened risk of cancer recurrence associated with immunosuppression used after transplantation. In recent years, older patients are being accepted for transplantation. The purpose of this study was to investigate overall and cause-specific mortality in kidney transplant patients with a history of malignancy, to evaluate overall survival and cancer-related outcomes. We conducted a retrospective descriptive study collecting all cases of kidney transplanted patient with cancer history in the nephrology department over a period of forty years A total of three patients with cancer history underwent a kidney transplantation Case 1. A 56-year-old man underwent kidney transplantation because of bilateral nephrectomy. Right nephrectomy indicated in front of non-functional lithiasis kidney and a left nephrectomy indicated in front of vesical tumor invasion. Sixteen years before the transplant he was diagnosed as having a vesical tumor GII PT1. During his nine years of follow up he has had an episode of urinary infection, an episode of rejection and an episode of endocarditis. There has been no recurrence of malignancy. Case 2. A 45-year-old women underwent kidney transplantation because of vascular nephropathy. Two years before the transplant she underwent a thyroidectomy as treatment of papillary thyroid carcinoma and since then he has been considered cured. During her three years of follow up she has had an episode of rejection, an episode of urinary infection, a serous cystadenoma after one year of transplantation indicated the switch by sirolimus and cortico-induced diabetes. There has been no recurrence of malignancy. Case 3. A 65-year-old women underwent kidney transplantation because of chronic glomerular nephropathy. Eleven years before the transplant she underwent a radical mastectomy followed by hormonal therapy as treatment for breast cancer. During her five years of follow up she has had many episode of urinary infection, cortico-induced diabetes and an episode of ischemic cerebrovascular accident. There has been no recurrence of malignancy. Our findings indicate that there is no significant morbidity from recurrence cancer and no development of secondary type of cancers in pre-existing malignancies. But we must be careful about risk of rejection. The factors that should be considered in each individual case are the type and extent of cancer and the duration between diagnosis and the proposed transplant.

P0465NEPHROTIC SYNDROME IN ELDERLY PATIENTS

Abstract Background and Aims Nephrotic syndrome (NS) is one of the manifestations of acute or chronic glomerular nephropathy in the elderly. Our study objective was to determine the particularities of NS in the elderly. Method This is a retrospective study, carried out in the Internal Medicine department A of Charles Nicolle hospital at Tunis, between January the 1st, 1975 and December the 31st, 2016. This study included subjects aged 65 years old or over hospitalized for NS. Results We studied 115 patients with an average age of 71 ± 5 years [65-83 years] with a sex ratio (M/F) of 1.7. Twenty-three percent of patients were diabetic. The median proteinuria was 4.7 g/l [3-19.5 g/l], the mean albumin level was 20 ± 6g/l and the mean protidemia was 50.6 ± 6.9 g/l. Nephrotic syndrome was impure in 89.5 % of patients with high blood pressure in 54 % of cases, hematuria ≥2 + in 30% of cases and renal failure in 82.7 % of cases. Renal biopsy was performed in 45 patients. The most common glomerular lesions were Membranous nephropathy (29 %) followed by amyloidosis (24.5 %). NS was secondary in 65.2 % of cases mainly to amyloidosis (35.6 %) and diabetes (19 %). Idiopathic nephropaty was dominated by membranous nephropathy (9.5 %) and primitive primitive (MPGN) (4.3 %). The treatment was symptomatic for 84.4% of patients. Corticosteroids and/or immunosuppressive treatment have been used for 15.6% of patients. At the end of follow-up, 35.3 % of patients achieved complete or partial remission and 56.6 % progressed to ESRD. Conclusion Elderly NS was characterized by a poor prognosis due to delayed cosultation and non-uniform treatment strategies. Multicentric study in order to identify different action axes could improve the prognosis of this disease. Multicentric study in order to identify different action axes could improve the prognosis of this disease.

Solid Organ Cancer and Melanoma in Kidney Transplant Recipients: TumorTx Base Preliminary Results

BackgroundIncidence of malignancy in transplant recipients is higher than in the general population. Malignancy is a major cause of mortality following solid organ transplantation and a major barrier to long-term survival for the kidney. The aim of this study was to estimate the incidence of solid organ malignancy (SOM) and melanoma in renal transplant recipients (RTR) transplanted at 2 representative transplant centers in Poland based on data from the Polish Tumor Registry. Material and MethodsWe analyzed the medical data of 3069 patients who underwent kidney transplantation (KTx) between 1995 and 2015. ResultsIn our study 112 SOM (3.6%) were diagnosed. The majority of patients were male (n = 71; 63.4%; P < .01). The mean age at KTx was 48.0 ± 13.1 years and the mean age at the time of cancer diagnosis was 55.9 ± 12.7 years. The average time of malignancy occurrence was 5.9 ± 5.0 years after KTx. SOM was the cause of death in 60 patients (53%). The most common were malignancies of gastrointestinal tract (25%), urinary tract tumors (23.2%), lung cancer (n = 18; 16%), and lymphoma (13.4%). We found an increase in the percentage of chronic glomerular nephropathy in the group of SOM (n = 56; 50%) compared with renal insufficiency of other etiologies. ConclusionsRTR in Poland are at a significant risk of malignancy development in a variety of organs, primarily urinary tract tumors and lymphoma. Cancers most frequently occurring in the general population such as lung and colorectal cancer are common in our RTR. On this basis an appropriate tumor screening schedule can be developed in individual countries.

Amylose AA

AA amyloidosis remains one of the three main types of systemic amyloidosis with AL and ATTR. Its incidence has been however decreasing recently in Western countries. Chronic inflammatory diseases are currently the first cause of AA amyloidosis, including rheumatoid arthritis, spondyloarthritis and autoinflammatory diseases. Castleman's disease is a specific cause of AA amyloidosis that can be cured by surgery. A chronic inflammatory response is required to develop amyloidosis. Other genetic and environmental factors are also involved. The first clinical manifestation is a chronic glomerular nephropathy, which can be detected by urine examination and serum creatinine measure. Immunohistochemistry is mandatory to confirm the clinical diagnosis of AA amyloidosis and to avoid misdiagnosis. Long-term prognosis remains poor on chronic dialysis in case of clinical gut involvement. Current treatment is based on the control of the inflammatory response. Specific treatment aimed at inhibiting amyloid formation targeting serum amyloid P component and heparan sulphate are currently evaluated.

Renal impairment in multiple myeloma: A single center experience.

To determine the features of the different forms of kidney diseases associated with multiple myeloma (MM), we retrospectively studied 144 patients with kidney injury and MM at our institute from 1974 to 2014. The mean age of the patients was 60.1 years and the male:female ratio was 1.25. Renal disease was concomitant with the discovery of MM in 92% of cases. The mean follow-up of our patients was 2.1 years. Initial renal insufficiency was found in 131 (91%) patients. Cast nephropathy of the distal tubule was found in 110 (26%) patients, renal amyloidosis in 16 (11.1%), and light chain deposition disease in five (3.47%). Twelve (8.3%) patients had chronic glomerular nephropathy. Twenty-six patients reached end-stage renal failure within 13.4 months. Renal survival was 30.45 months. Predictive factors for improvement of renal function undergoing chemotherapy included serum creatinine <250 µmol/L, proteinuria <1 g/24 h, and the non-use of renal replacement therapy. Multiple pathogenic mechanisms can contribute to kidney injury in myeloma patients. Novel myeloma agents have shown considerable promise in reversing renal failure in some patients and improving outcomes.

P3-24: Secondary hypertension in a tunisian internal medicine department

Secondary hypertension (SH) refers to arterial hypertension due to an identifiable and often curable cause. It affects approximately 5-10% of the general hypertensive population. SH can be caused by conditions that affect kidneys, arteries, heart or endocrine system. Our aim is to describe the different causes of SH noted in our patients. It is a retrospective study of 240 patients followed for a SH at the Internal Medicine Department of the Tunisian Military Hospital from 2000 to 2015. The diagnosis of SH in these patients was suspected in front of clinical and biological arguments and confirmed by the further explorations guiding a suitable therapeutic attitude. Renal causes were the main etiology of SH (233 patients) with acute glomerular nephritis (AGN) in 4 cases, primary chronic glomerular nephropathy (CGN) in 14 cases, including 8 cases of membranous glomerulonephritis, 2 cases of focal segmental glomerulosclerosis and 4 cases of membrano-proliferative glomerulonephritis. Secondary CGN were dominated by diabetic nephropathy in 174 cases, lupus nephropathy in 10 cases and rheumatoid purpura in one case. Congenital kidney diseases were represented by hereditary polycystic kidney disease in 20 patients and Alport syndrome in 2 patients. The renovascular hypertension was noted in 8 cases. The endocrine causes were present in 6 patients (2 cases of Conn syndrome, 2 cases of hyperthyroidism, 1 case of bilateral adrenal hyperplasia and another case of pheochromocytoma). One patient had SH with a cardiac cause that was aortic coarctation. The prevalence of SH exceeds 30% among patients with resistant hypertension. Common causes include chronic kidney diseases, primary aldosteronism, renovascular hypertension and obstructive sleep apnea. In our study, renal parenchymal disease particularly diabetes is the most common cause of SH. Physicians should be judicious about evaluation of a potentially curable cause of hypertension. Careful clinical evaluation and simple algorithms help avoid unnecessary investigations. In patients with SH, early detection and treatment are important to minimize and prevent irreversible changes in the vasculature and target organs.

Metabolic responses during hemodialysis determined by quantitative 1H NMR spectroscopy

A large proportion of patients with end-stage renal disease have lifelong hemodialysis (HD) treatment. HD rapidly and indiscriminately removes necessary small metabolites together with uremic toxins from plasma into dialysate. To investigate metabolic responses to HD, we determined the levels of metabolites through time-course monitoring of 1H NMR spectroscopy of dialysate during HD. The dialysate sample is stable for analysis because it contains only small metabolites without proteins. It was collected non-invasively from 9 HD patients with chronic glomerular nephropathy, at 6 time points during 4h of HD in 5 sessions. Creatinine, alanine, lactate, pyruvate and valine were simultaneously quantified on a one-dimensional single-pulse spectrum with a single standard compound. The concentration of creatinine exhibited monotonous decay with time, while that of valine decreased slowly and then maintained its levels throughout an HD. Lactate, alanine and pyruvate increased at 2–3h after the initiation of HD. They exhibited remarkable responses to HD with production from the body. The time-course of change in the 4 metabolites of lactate, pyruvate, alanine, and valine had reproducible behavior unique to each patient during the HD. This finding may be applied to distinguish metabolic status in HD patients.

The effect of vitamin E-bonded polysulfone membrane dialyzer on a new oxidative lipid marker.

The use of vitamin E-bonded cellulose membrane dialyzers has been reported to cause a decrease in oxidative lipid marker levels (Nakai et al., Ther Apher Dial 14:505–540, 1; Nakai et al., J Jpn Soc Dial Ther 45:1–47, 2; Mashiba et al., Arterioscler Thromb Vasc Biol 21:1801–1808, 3). However, few studies have identified this effect with vitamin E-bonded polysulfone membranes, and no studies report the same effect on alpha (1) antitrypsin–LDL complex, a new oxidative lipid marker. This prompted us to examine the influence of use of VPS-HA vitamin E-bonded polysulfone high-flux membrane dialyzers on this new oxidative lipid marker. The subjects were 17 patients who had been dialyzed with VPS-HA for 12 months. The subjects’ baseline characteristics were as follows. Their average age was 65.6 ± 13.1 years, comprising 8 males and 9 females; hemodialysis vintage was 83.8 ± 85.4 months. Eight had chronic glomerular nephropathy and five had diabetic nephropathy. The primary outcome was defined as alpha (1) antitrypsin–LDL complex level after 12 months, as a post-study using VPS-HA. Secondary outcomes included triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol levels. The data were analyzed pre-study and after 3, 6, 9 and 12 months for alpha (1) antitrypsin–LDL complex, and pre-study and post-study for the other indicators. Twelve months after switching to VPS-HA, alpha (1) antitrypsin–LDL complex, total cholesterol and LDL cholesterol had significantly decreased. Triglycerides and HDL cholesterol had not significantly changed. Hemodialysis therapy with VPS-HA was shown to decrease alpha (1) antitrypsin–LDL complex, an index of oxidative stress, and also to decrease some lipid markers.

Presence of ochratoxin A in Tunisian blood nephropathy patients. Exposure level to OTA

Ochratoxin A (OTA) produced by Aspergillus and Penicillium genera contaminates cereals and different food compounds. OTA presents a wide range of toxic effects, especially nephrotoxicity. It is also considered to be the main causal agent of Balkan Endemic Nephropathy (BEN) which is similar to the Chronic Interstitial Nephropathy with unknown aetiology seen in Tunisia. In this study, we attempted to confirm the relationship between OTA blood levels and the development of renal pathology. Hence, serum OTA levels were measured in several groups of patients having different renal diseases: a group presenting Chronic Interstitial Nephropathy (CIN) with unknown aetiology, a group presenting Chronic Interstitial Nephropathy (CIN) with known aetiology, a group presenting Chronic Glomerular Nephropathy (CGN), and a group presenting Chronic Vascular Nephropathy (CVN). Each group was compared to a healthy control group. In the healthy group, 49% of individuals showed OTA concentrations ranging from 1.7 to 8.5 ng/ml, with a mean value of 3.3 ± 1.5 ng/ml. However, among nephropathic patients, the group with CIN of unknown aetiology showed the highest incidence (76%), ranging from 1.8 to 65 ng/ml with a mean value of 18 ± 7 ng/ml. Even in the healthy group, the calculated Daily Intake (DI) ranged from 5.0 to 24.9 ng/kg b.w./day when compared to the recommended DI by the scientific committee on foods of 5 ng/kg b.w./day, indicating a high degree of exposure to OTA in the Tunisian population. Our study confirms the involvement of this nephrotoxic mycotoxin, present at high blood levels in the Tunisian population, in the outcome of this particular human nephropathy (CIN with unknown aetiology) which is similar to BEN.

Serum levels of ochratoxin A in healthy subjects and in nephropathic patients in Tunisia.

Ochratoxin A is a fungal toxin produced by Aspergillus and Penicillinium. These Fungi oftenly contaminate plant-derived products, and can generate deleterious toxic effects in man. In this study, ochratoxin A was determined in human serum samples collected in Tunisia, using high performance liquid chromatography (HPLC) and fluorescence detection. The samples were collected from healthy subjects (n = 105) as well as from patients with various kidney disorders. Five different kinds of kidney disorders were represented: transplanted subjects (27), patients with Chronic Interstitial Nephropathy (22) of known etiology, Chronic Vascular Nephropathy (26), Chronic Glomerular Nephropathy (26) or Chronic Interstitial Nephropathy (30) of unknown etiology. Mean concentrations of ochratoxin A in the healthy group was 0.49+/-0.79 ng/mL. The highest mean concentration of ochratoxin A was found in group of Chronic Interstitial Nephropathy of unknown etiology 1.25+/-1.22 ng/mL. Significant differences were also observed according to the geographic origin of healthy subjects and nephropthic patients within Tunisia.

Ochratoxin A in human blood in relation to nephropathy in Tunisia

The determination of ochratoxin A (OTA) in human blood in Tunisian populations is underway. The range of contamination is between 0.7 to 7.8 ng ml-1 for the general population and 12 to 55 ng ml-1 for people suffering from chronic renal failure. It appears that 21 to 64% of people suffering from nephropathy are OTA positive with a detection limit of 1ng ml-1. This situation prompted us to search for possible association of OTA contamination and nephropathy resembling Balkan endemic nephropathy. The classification of the ill population into chronic interstitial nephropathy (CIN), chronic glomerular nephropathy (CGN), chronic vascular nephropathy (CVN) and others, indicated that the largest is the CIN group which is significantly different from the other groups, and from the control (P < 0.005). Furthermore, it presented the highest OTA mean values (25 to 59 ng ml-1) compared with the control, CGN, CVN and other groups (6 to 18 ng ml-1) according to the designated region in Tunisia. The rural population seems to be more exposed to ochratoxins in Tunisia, as has been previously reported in the Balkans and Western Europe. Altogether, these results emphasise that in Tunisia an endemic ochratoxin-related nephropathy is probably occurring.