Serum ferritin as an activity marker for granulamotosis with polyangiitis

Background: Serum ferritin correlates well with the activities of systemic lupus erythematosus (SLE) and dermatomyositis, but it has not been previously studied in patients with vasculitis.

Methods: Medical records of granulomatosis with polyangiitis (GPA, Wegener’s granulomatosis) patients with at least six months of regular follow-up were evaluated. The activity of GPA was assessed with Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BVAS/WG). Serum ferritin and other acute phase markers were measured at initial presentation.

Results: Serum ferritin levels were found to be the highest in GPA patients with alveolar hemorrhage, median (IQR) 1041 (1281) μg/L. Patients with renal disease also had high levels of ferritin and it was correlated with concurrent glomerular filtration rate (r?=??0.65, p?r?=?0.79, p?Conclusions: Measurement of serum ferritin might help in assessing disease activity of GPA.     

The relationship between proteinuria and allograft survival in patients with transplant glomerulopathy: a retrospective single-center cohort study

Proteinuria and transplant glomerulopathy (TG) are common in kidney transplantation. To date, there is limited knowledge regarding proteinuria in different types of TG and its relationship to allograft survival. A retrospective cohort analysis of TG patients from indication biopsies was performed to investigate the relationship of proteinuria, histology, and graft survival. One hundred and seven (57.5%) out of 186 TG patients lost their grafts with a median survival of 14 [95% confidence interval (CI) 10–22] months after diagnosis. Proteinuria ≥1 g/24 h at the time of biopsy was detected in 87 patients (46.8%) and the median of proteinuria was 0.89 (range 0.05–6.90) g/24 h. TG patients with proteinuria ≥1 g/24 h had worse 5-year graft survival (29.9% vs. 53.5%, P = 0.001) compared with proteinuria <1 g/24 h. Proteinuria was associated with graft loss in univariable Cox regression [hazard ratio (HR) 1.25, 95% CI, 1.11–1.41, P < 0.001], and in multivariable analysis (adjusted HR 1.26, 95% CI 1.11–1.42, P < 0.001) independent of other risk factors including creatinine at biopsy, positive C4d, history of rejection, and Banff lesion score mesangial matrix expansion. In this cohort of TG patients, proteinuria at indication biopsy is common and associated with a higher proportion of graft loss.     

Oxidative stress and ferritin levels in haemodialysis patients.

BACKGROUND: Increased oxidative stress (OS) and inflammation are associated with atherosclerotic coronary artery disease in haemodialysis (HD) patients. Ferritin may have other effects in addition to its role in storing intracellular iron. This study was performed to determine any relationships between markers of OS, nutrition and inflammation in HD patients with normal and high ferritin levels. METHODS: Our cohort comprised 34 maintenance dialysis patients on erythropoietin therapy and 22 healthy controls. HD patients were divided into two groups: 17 with normal (<800 ng/ml) and 17 with high (>800 ng/ml) ferritin levels, and we measured lipid profile, albumin, highly sensitive C-reactive protein (hsCRP), anti-oxidant enzymes [whole blood glutathione peroxidase (Gpx), serum superoxide dismutase (SOD), paraoxonase, arylestherase (AE) and total anti-oxidant status (TAOC)], anti-oxidants (vitamin C) and lipid peroxidation products [red blood cell malondialdehyde (RBC MDA)]. RESULTS: Compared with controls, the HD patients had higher serum urea, blood pressure, triglyceride, hsCRP, RBC MDA, SOD and TAOC values and lower albumin, low-density lipoprotein cholesterol, apolipoprotein AI, paraoxonase, AE and whole blood Gpx activities. Serum vitamin C, uric acid, apolipoprotein B, total- and high-density lipoprotein cholesterol, apolipoprotein B MDA, and lymphocyte levels in the HD patients with normal and high ferritin levels were similar. The OS markers of HD patients did not differ, whether or not they received intravenous iron supplementation or had transferrin saturations < 50% or > or = 50%. CONCLUSION: HD patients are in a higher oxidative state, which results in the reduction of total anti-oxidant capacity and also have an increased inflammation status. We could not find a relationship between ferritin level and OS markers in HD patients receiving erythropoietin.     

Transforming growth factor-beta(1) in the kidney and urine of patients with glomerular disease and proteinuria.

BACKGROUND: Transforming growth factor-beta(1) (TGF-beta(1)) is the major fibrogenic growth factor implicated in the pathogenesis of renal scarring. Proteinuria is a poor prognostic feature for various types of glomerular disease and its toxic action may be related to the activation of tubular epithelial cells towards increased production of cytokines and chemoattractant peptides. In this work we studied the site of synthesis and expression profile of TGF-beta(1) in the renal tissue of patients with heavy proteinuria and examined the relation of this expression with the urinary excretion of TGF-beta(1). METHODS: Twenty-five patients with heavy proteinuria (8.4+/-3.0 g/24 h) were included in the study. All patients underwent a diagnostic kidney biopsy and were commenced on immunosuppressive therapy with corticosteroids and cyclosporin. The sites of synthesis and expression profile of TGF-beta(1) mRNA and protein in the kidney were examined by in situ hybridization and immunohistochemistry. Urinary and plasma TGF-beta(1) levels were determined by ELISA before the initiation of treatment and 6 months later and compared with those of normal subjects and of patients with IgA nephropathy and normal urinary protein excretion. RESULTS: The site of synthesis and expression of TGF-beta(1) in the renal tissue of patients with heavy proteinuria was mainly localized within the cytoplasm of tubular epithelial cells. Interstitial expression was also present but glomerular TGF-beta(1) expression was found only in patients with mesangial proliferation. Urinary TGF-beta(1) excretion was significantly higher in nephrotic patients compared with normal subjects and with patients with IgA nephropathy and normal urinary protein excretion (783+/-280 vs 310+/-140 and 375+/-90 ng/24 h, respectively; P<0.01). In patients with remission of proteinuria after immunosuppressive therapy, urinary TGF-beta(1) excretion was significantly reduced (from 749+/-290 to 495+/-130 ng/24 h; P<0.01), while in patients with persistent nephrotic syndrome, it remained elevated. CONCLUSIONS: The localization of TGF-beta(1) mRNA and protein within tubular epithelial cells, along with its increased urinary excretion in patients with nephrotic syndrome, suggest the activation of these cells by filtered protein towards increased TGF-beta(1) production.     

Structural alterations to the podocyte are related to proteinuria in type 2 diabetic patients.

BACKGROUND: The podocyte is believed to play a key role in maintaining the integrity of the glomerular filtration barrier, and damage or loss has been linked to the development of albuminuria. METHODS: Renal biopsies from 16 type 2 diabetic patients with nephropathy and 28 non-diabetic controls were analysed using light and electron microscopy. RESULTS: Podocyte number per glomerulus was significantly lower in the type 2 patients compared with controls [mean (95% confidence interval) 464 (382-546) vs 589 (543-635), P = 0.004]. Mean glomerular volume was significantly increased in diabetic patients compared with controls [5.5 (4.9-6.1) vs 3.1 (2.7-3.5) x 10(6) microm(3), P<0.001], thus the diabetic patients demonstrated an even greater proportional reduction in podocyte density per glomerulus [88 (68-108) vs 201 (182-220)/10(6) microm(3), P<0.001]. Podocyte foot process width on both the filtration surface (FPWgbm) and mesangial surface (FPWmes) was significantly increased compared with controls [796 (708-884) vs 556 (460-908) nm, P = 0.001; 1108 (821-1394) vs 760 (555-1078) nm, P = 0.029, respectively]. There was a significant negative correlation between proteinuria and both podocyte number and podocyte density per glomerulus (r = -0.63, P = 0.009; r = -0.58, P = 0.018, respectively). There was a significant positive correlation between proteinuria and both FPWgbm and FPWmes (r = 0.64, P = 0.008, for both). CONCLUSION: Podocyte loss occurs in type 2 diabetic nephropathy and is related to increasing proteinuria. Whether the accompanying glomerular enlargement and widening of foot processes are a cause of podocyte loss is uncertain. Longitudinal studies are required to determine the sequence of events leading to podocyte loss in diabetic nephropathy.     

High proteinuria selectivity index based upon IgM is a strong predictor of poor renal survival in glomerular diseases.

BACKGROUND: The transport of large proteins across the glomerular capillary wall (GCW) may increase several fold in glomerular diseases. The occurrence of IgM in urine is a consequence of the presence of large defects or shunts in the GCW, whereas albuminuria is probably a result of an altered charge- and size-selectivity of the GCW. In order to examine whether patho-morphological differences influence the renal outcome in proteinuric glomerulopathies, we examined urinary excretion of IgM and albumin as prognostic markers of glomerular disease. METHODS: An observational study over a median of 41 (+/-3) months was conducted in 84 patients with biopsy-verified glomerular disease. The patients were subdivided into groups with low (< or =0.002) and high (>0.002) proteinuria selectivity index based upon IgM (IgM-SI), and into groups with low (< or =200 mg/mmol) and high (>200 mg/mmol) albumin creatinine index (ACI). RESULTS: In the high IgM-SI group, the median creatinine clearance (Ccr) decreased by 26%, and 62% of the patients decreased in Ccr by >5 ml/ min/year during the follow-up time. In comparison, the median Ccr decreased by 8% in the low IgM-SI group (P<0.001) and only 18% of the patients in this group deteriorated by >5 ml/min/year in the Ccr. Eleven (21%) of the 51 patients in the high IgM-SI group developed end-stage renal failure compared with none of the 33 patients in the low IgM-SI group. All the patients that progressed to uraemia had decreased Ccr (<60 ml/min) at entry into the study. However, among all these patients, only those with high IgM-SI, and none with low IgM-SI, developed end stage renal failure. The fall in Ccr did not differ significantly between the patients in high (12%) and low (16%) ACI groups. CONCLUSION: The results of this study indicate that an increased IgM-SI value is a stronger predictor of clinical outcome in proteinuric glomerulopathies than baseline albuminuria. This finding may reflect different patho-histological mechanisms influencing renal survival in glomerular diseases.     

Lovastatin in glomerulonephritis patients with hyperlipidaemia and heavy proteinuria.

Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor, was given to 14 patients with unremittent nephrotic syndrome (heavy proteinuria with hyperlipidaemia) for 6 months. Treatment was started at an initial dose of 20 mg/day, increasing to a maximum of 80 mg/day. Treatment was well tolerated except in two patients: one developed rhabdomyolysis and one severe hypertriglyceridaemia requiring an additional antihyperlipidaemic agent. Lovastatin was effective in reducing serum cholesterol, LDL-C and apolipoprotein B in the remaining 12 patients. Cholesterol was reduced by 31% from 8.24 +/- 0.49 mmol/l (mean +/- SEM) to 5.7 +/- 0.18 mmol/l after 6 months (P less than 0.001). LDL-C was normalized to 3.26 +/- 0.21 mmol/l from a pretreatment value of 5.76 +/- 0.48 mmol/l (P less than 0.001), a decrease of 43%. Serum apolipoprotein B was also normalized to 1.11 +/- 0.09 g/l from a basal level of 1.51 +/- 0.10 g/l (P less than 0.05). Triglyceride, HDL-C and apolipoprotein A1 concentrations were unchanged. Proteinuria as well as renal albumin clearance were unchanged. GFR by plasma radioisotope Cr-EDTA clearance for the whole group was unaltered by treatment. However, among those with relatively good pretreatment renal function (GFR greater than 70 ml/min per 1.73 m2), GFR increased at the end of 6 months' treatment (118.2 +/- 15 ml/min per 1.73 m2 versus 77.6 +/- 8.4 ml/min per 1.73 m2 in wash-out phase).(ABSTRACT TRUNCATED AT 250 WORDS)     

Symptomatic antiproteinuric treatment decreases serum lipoprotein (a) concentration in patients with glomerular proteinuria

Elevated serum levels of the atherogenic and thrombogenic lipoprotein(a) (Lp(a)) have been recognized as a feature of the nephroticsyndrome associated hyperlipidaemia. To examine a possible relationshipbetween serum Lp(a) concentration and proteinuria, serum albumin,or blood pressure, we studied nine patients with nephrotic-rangeproteinuria both at baseline and after various forms of antihypertensiveand antiproteinuric treatment. In fixed order, patients receivedconventional antihypertensive treatment (either -methyldopaor clonidine), subsequently ACE-inhibition therapy (lisinopril),ACE inhibition combined with an NSAID (indomethacin), and finallyNSAID plus conventional antihypertensive therapy. Measurementswere performed at the end of each 2-month study period. When compared to controls (n = 29), proteinuric patients beforetreatment showed increased levels of total cholesterol, very-lowand low-density lipoprotein (VLDL + LDL) cholesterol, triglyceridesand apolipo-protein B (apoB), while high-density lipoprotein(HDL) HDL cholesterol was lower. Lp(a) was significantly higherin patients (107 (95% CI: 55–208) mg/l) as compared tocontrols (25 (13–49) mg/l, P<0.01). Conventional antihypertensivetreatment did not reduce proteinuria, while Lp(a) remained unaffected.ACE-inhibitor treatment lowered proteinuria, raised serum albumin,while La(a) tended to fall (– 11 ±8%). Additionof an NSAID induced a further fall in proteinuria and a risein serum albumin. Lp(a) now fell by 40±5% from baselinevalues (P<0.01). Both serum total, HDL and VLDL + LDL cholesterolfell significantly. Finally, during subsequent single therapywith NSAID most parameters, including proteinuria and Lp(a),returned towards values obtained during single therapy withACE inhibition. Multiple regression analysis showed a strongrelation of Lp(a) with the amount of proteinuria (P = 0.001),while serum albu-min did not independently contribute to Lp(a)levels (P = 0.2). In conclusion, effective symptomatic antiproteinuric treatmentdecreases serum Lp(a) levels in patients with glomerular proteinuria.Our data suggests that renal protein leakage plays a more importantrole in the metabolic regulation of this lipoprotein than serumalbumin level, and that antiproteinuric treatment may be ofbenefit in reducing the increased risk of thrombosis and atherosclerosisobserved in this patient category.     

Adiponectin is increased and correlated with the degree of proteinuria, but plasma leptin is not changed in patients with chronic glomerulonephritis

Aim:   Altered regulation of adiponectin and leptin may be relevant to endothelial dysfunction and cardiovascular complications in patients with chronic glomerulonephritis.
Methods:   The relationship between the levels of plasma adiponectin, leptin and proteinuria, glomerular filtration rate and metabolic risk factors was investigated in 38 patients with chronic glomerulonephritis.
Results:   Plasma adiponectin was much higher in patients with heavy proteinuria (38.8 ± 27.8 µg/mL) than in patients with mild proteinuria (13.3 ± 5.1 µg/mL, P  < 0.001) and with moderate proteinuria (18.1 ± 8.0 µg/mL, P  < 0.01). The levels of serum leptin were not changed among these groups. Proteinuria and lipoprotein(a) were a strong and direct correlate of plasma adiponectin ( r  = 0.75, P  < 0.0001), while serum albumin and the glomerular filtration rate correlated inversely with this protein ( r  = −0.56, P  = 0.0002; r  = 0.38, P  = 0.02). Body mass index and triglyceride were direct correlates ( r  = 0.37, P  = 0.02 and r  = 0.37, P  = 0.02, respectively) of plasma leptin in patients with glomerulonephritis.
Conclusions:   Plasma adiponectin but not plasma leptin levels correlate with proteinuria in patients with chronic glomerulonephritis.     

Glomerular immune deposits are associated with increased proteinuria in patients with ANCA-associated crescentic nephritis.

BACKGROUND: In small vessel vasculitis and its renal-limited form, idiopathic crescentic glomerulonephritis, renal damage is characterized by pauci-immune necrotizing crescentic glomerulonephritis (CGN) without histological evidence of immunoglobulin (Ig) deposition. In some patients, however, significant amounts of immune deposits may be detected. Therefore, we evaluated the clinical significance of these immune deposits in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune CGN. METHODS: Renal biopsies of 45 consecutive patients with new onset of Wegener's granulomatosis, microscopic polyangiitis and idiopathic CGN were retrospectively evaluated by light microscopy, immunohistochemistry and electron microscopy and the findings compared with renal function and outcome. RESULTS: Typical pauci-immune CGN was found in 37 patients (group I). In eight patients (18%; group II), however, histopathological examination revealed substantial deposition of Ig in the mesangium and/or along the glomerular basement membrane. Five of these eight patients were cANCA positive; two initially had pANCA and developed a cANCA pattern and one was pANCA positive. There were no differences between groups in age, gender, renal function or extra-renal organ involvement at the time of biopsy. However, patients in group II had significantly more proteinuria (5.4+/-3.1 vs 1.3+/-1.0 g/24 h; P=0.016). We also observed a trend for a worse outcome with respect to renal function and mortality in group II patients; however, the differences did not reach significance. CONCLUSIONS: Our results confirm that in ANCA-associated CGN a substantial percentage of patients have evidence of Ig deposition in renal biopsies. In this subgroup, Ig deposition was associated with a significantly greater degree of proteinuria. Further investigations are necessary to define the full clinical impact of immune-complex deposition on the clinical course of renal disease in pauci-immune CGN.     

血清铁蛋白水平与骨密度的相关性研究

目的分析绝经后女性及50岁以上男性不同骨量人群血清铁蛋白的差异,探讨血清铁蛋白水平与骨密度的相关性。 方法选择2018年9月至2019年2月期间于河北医科大学第三医院就诊,接受双能X线骨密度测量仪（DEXA）检测骨密度（BMD）的绝经后女性（131例）及50岁以上男性（65例）患者（共196例）,根据BMD分为骨量正常组（46例）、骨量减少组（68例）和骨质疏松组（82例）。收集上述患者的临床资料,检测相关生化指标,并测定血清铁蛋白水平,评估血清铁蛋白与骨密度的相关性。 结果（1）与骨量正常组[99.50（91.55,128.51）ng/ml]和骨量减少组[103.36（93.26,113.46）ng/ml]相比,骨质疏松组血清铁蛋白水平明显增高[（174.25（160.85,210.42）ng/ml）（χ²=100.573,P=0.000）。（2）血清铁蛋白水平与髋部、腰椎骨密度均呈负相关,（髋部r=-0.487,P<0.05;腰椎r=-0.531,P<0.05）。（3）体重为骨质疏松症的保护因素（r=0.049,P<0.05）,血清铁蛋白为骨质疏松症的危险因素（r=-0.018,P<0.05）。 结论血清铁蛋白水平增高是骨质疏松症的危险因素,在骨质疏松症的发生中可能起重要作用。     

肺癌患者血清铁蛋白的表达及临床意义

目的探讨肺癌患者血清铁蛋白的表达及临床意义。方法收集并检测174例肺癌患者和85例肺良性病变患者术前血清铁蛋白水平,并分析血清铁蛋白水平与肺癌临床病理特征间的关系。结果肺癌患者血清铁蛋白显著高于肺良性病变患者,鳞癌、肿瘤较大、低分化和晚期的非小细胞肺癌患者血清铁蛋白分别显著高于腺癌、肿瘤较小、高一中分化和早期的患者。结论血清铁蛋白可能在肺癌的发生和进展中起到促进作用。     

Serum and urinary high density lipoproteins in glomerular disease with proteinuria

The serum lipoprotein concentrations, including high-density lipoprotein (HDL) subfractions and apolipoproteins Al and B were measured in 21 patients (14 male and seven female) with nephrotic range proteinuria (greater than 3g/24hr), well maintained renal function (creatinine clearance greater than 35 mliter/min/1.73m2) and biopsy-proven primary glomerular disease. In these, and in a further five patients (creatinine clearance greater than 15 mliter/min/1.73m2), urinary apolipoprotein Al output was determined. Total HDL cholesterol was similar in patients and controls, but in male patients, HDL2 was low (0.54 +/- 0.10 mmole/liter, mean +/- SEM) compared to controls (0.75 +/- 0.04 mmole/liter, P less than HDL3 was high (0.81 +/- 0.07 in patients and 0.63 +/- 0.02 mmole/liter in controls, P less than 0.01). In women, there was a similar tendency for HDL2 to be lower in patients (0.68 +/- 0.18 mmole/liter) than in controls (0.85 +/- 0.10 mmole/liter). Multiple regression analysis revealed that major determinants of the urinary apolipoprotein Al output were the urinary protein output and selectivity index (multiple r = 0.85). Furthermore, some patients lost apolipoprotein Al into their urine at rates indicating increased production of apolipoprotein Al in the nephrotic syndrome. The serum HDL subfraction concentrations in the nephrotic syndrome could be explained by a combination of increased HDL production and increased urinary loss of low molecular wt HDL.     

Conversion from calcineurin inhibitors to sirolimus in chronic allograft dysfunction: changes in glomerular haemodynamics and proteinuria.

BACKGROUND: The study was conducted in order to describe possible intraglomerular haemodynamic changes inducing proteinuria after 14 patients with chronic allograft dysfunction were converted from calcineurin inhibitors (CIs) to sirolimus without changing concomitant immunosuppression or antihypertensive treatment. METHODS: Creatinine, glomerular filtration rate (GFR), proteinuria, renal functional reserve (RFR) and effective renal plasma flow (ERPF) were determined before and 8 months after conversion. Intraglomerular pressure (P(G)), afferent arteriolar resistance (AAR) and efferent arteriolar resistance (EAR) were calculated using Gomez's formula. RESULTS: Creatinine (1.97 vs 2.075 mg/dl; P = 0.270) and GFR (40 vs 43 ml/min; P = 0.505) remained unchanged, proteinuria increased (338 vs 1146 mg/24 h; P = 0.006), RFR decreased (34.84 vs 13.47%; P = 0.019), ERPF (248 vs 310.6 ml/min; P = 0.0625) and P(G) (42.72 vs 46.17 mmHg; P = 0.0625) tendentially increased and AAR tendentially decreased (14.12 vs 10.28 dyne/s/cm(5); P = 0.0625). CONCLUSION: After conversion, P(G) shows a tendency to increase and RFR decreases significantly-characteristics of hyperfiltration, which could possibly partially explain the increase of proteinuria. Therefore, the application of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers seems promising. To avoid hyperfiltration, conversion should be performed early when renal insufficiency is still moderate.     

Lack of clinical evidence for a specific HIV-associated glomerulopathy in 203 patients with HIV infection.

Several authors described a high incidence of proteinuria with frequent progression to nephrotic syndrome and/or renal failure in patients with HIV infection. Though renal histological changes were rather non-specific, the existence of a specific, HIV-associated glomerulopathy was postulated. We repeatedly investigated proteinuria and serum creatinine in 203 HIV-infected patients. One hundred and twenty-two patients (group 1) had early stages of the disease without opportunistic infections, 81 suffered from acute opportunistic infections (group 2). In patients with a positive qualitative test (Combistix), quantitative measurement (Biuret) for proteinuria was carried out; when proteinuria was greater than 0.5 g/24 h, SDS gel electrophoresis was performed. None of the patients of group 1 had a proteinuria greater than 0.5 g/24 h or an elevated serum creatinine. Eleven of 81 patients from group 2 had a proteinuria between 0.5 and 3 g/24 h; one further patient of group 2 developed a transient proteinuria of 7.7 g/24 h. Only three of the proteinuric patients showed a glomerular pattern in SDS gel electrophoresis, all three during acute CMV or EBV infections. Fourteen of 81 group 2 patients showed a transient elevation of serum creatinine (x +/- SD of the maximum serum creatinines: 225.3 +/- 163 mumol/l), most during pentamidine therapy for Pneumocystis carinii infection; one patient treated with high-dose acyclovir had to be temporarily dialysed. In the investigated 203 HIV patients no nephrotic syndrome and no sustained elevation of serum creatinine greater than 200 mumol/l was observed. All cases of proteinuria and elevation of serum creatinine were associated with severe opportunistic infections and the administration of potentially nephrotoxic antibiotics.