Mohamed M NasrAllah

OBJECTIVE:
The aim of the present study was to assess the effect of metabolic syndrome (MetS) and insulin resistance comorbidity on the carotid intima-media thickness (IMT) in systemic lupus erythematosus (SLE) patients and their relationship to clinical manifestations, disease activity, and damage.
METHODS:
The study included 92 SLE patients (mean age 30.18 ± 8.27 years) and 30 matched controls. Disease activity and damage were assessed by the SLEDAI and SLICC indices, respectively. The Health Assessment Questionnaire II (HAQII) and Quality of Life (QoL) index were evaluated in the patients. Levels of insulin, glucose, and creatinine and the lipid profile were measured in patients and controls. Insulin sensitivity was estimated using the homeostatic model assessment index (HOMA-B) for beta cell function and (HOMA-IR) for peripheral tissue insulin resistance. The carotid IMT was measured by ultrasonography.
RESULTS:
The SLE patients had high HOMA-IR and HOMA-B. The IMT was significantly increased (0.82± 0.29 mm) compared to the controls (0.45± 0.2 mm).The HOMA-IR, SLEDAI, SLICC, HAQII, and IMT were significantly higher and the QoL lower in those with MetS (n = 34) compared to those without (n = 58), while the HOMAB was comparable. There was a significant correlation between the IMT and the SLEDAI, SLICC, and WHR.
CONCLUSION:
Insulin sensitivity and IMT are altered in SLE patients, especially those with MetS comorbidity with an associated increase in disease activity and damage. Effective management of MetS would help control SLE activity, damage, and the future development of cardiovascular events especially in the absence of symptoms of cardiovascular disease.

BACKGROUND:
Advanced glycation end-products (AGE) accumulate in CKD and may predispose to cardiovascular disease by inducing inflammatory and oxidant stress in the vascular endothelium. Soluble forms of the receptor for AGE (RAGE) may be protective against these effects by binding AGE in the soluble phase. Accumulating evidence suggests a protective role of soluble RAGE against vascular calcification. This study investigates the association between endogenous soluble RAGE (esRAGE) and vascular calcification in hemodialysis patients.
METHODS:
We studied 65 non-diabetic hemodialysis patients, on 3 × 4 h dialysis schedule, and 19 controls. Serum levels of esRAGE, hsCRP, parathormone, lipids, calcium, and phosphorus were measured. Aortic calcification index (ACI) was measured using non-contrast CT of the abdominal aorta.
RESULTS:
Aortic calcification was detected in 64 out of 65 hemodialysis patients. Levels of esRAGE were lower in hemodialysis patients (278 pg/ml, SD 101.1) than in controls (443 ± 109 pg/ml; P = 0.001). ACI correlated negatively in stepwise multivariate analysis with esRAGE (P = 0.002) and positively with hsCRP (<0.0001), systolic blood pressure (P < 0.0001) and dialysis vintage (P = 0.05); R (2) = 0.65.
CONCLUSION:
Levels of esRAGE were low among hemodialysis patients and correlated negatively with ACI.

OBJECTIVES:

To verify the relation of gout to insulin resistance (IR) and metabolic syndrome (MetS) and find any association of metatarsophalangeal (MTP) joint erosions to the features of MetS and IR.

METHODS:

Forty-six primary gout male patients with a mean age of 41.96 ± 5.77 years were grouped according to the presence of MetS. Twenty-seven age and sex matched healthy volunteers served as controls. Insulin sensitivity was estimated using the homeostatic model assessment index (HOMA-B) for beta cell function and HOMA-IR for peripheral tissue IR.

RESULTS:

Gout patients had significantly higher HOMA-IR and HOMA-B compared to controls. Those with MetS (n = 27) had significantly higher serum uric acid (SUA) than those without (n = 19; 11.51 ± 3.72 mg/dL vs. 9.15 ± 2.34 mg/dL; P = 0.012). Gout patients with MTP erosions had notable higher insulin levels and more IR as shown by the higher levels of HOMA-IR and HOMA-B compared to those without. HOMA-IR and HOMA-B significantly correlated with the presence of erosions. Moreover, the presence of erosions significantly correlated with SUA (r = 0.64, P < 0.0001).

CONCLUSIONS:

The level of SUA is closely related to IR in patients with and without MetS. There is an association of the severity of gout and presence of MTP erosions to IR. Metabolic syndrome forms an important marker for those who develop more punched-out erosions.

Abstract
OBJECTIVE:
Renal vasculitis is usually associated with anti-neutrophil cytoplasmic antibodies (ANCAs). However, non-ANCA patients constitute a rarely studied variant of renal vasculitis. The aim of the present study was to demonstrate the features of renal involvement in patients with primary systemic non-ANCA associated vasculitis (NAAV) and compare essential cryoglobulinemic vasculitis (ECV) with classic polyarteritis nodosa (PAN).
METHODS:
The study included 30 patients with primary systemic non-ANCA associated vasculitis (NAAV). Fifteen with ECV and another 15 patients with classic PAN. The patients were recruited from the Rheumatology and Internal medicine departments and outpatient clinics of Cairo University Hospitals. The patients had no or mild renal involvement at entry and the ANCA was negative as tested by immunoflourescence and ELISA. Renal biopsy was performed for all the patients and histopathologically studied.
RESULTS:
Renal biopsy abnormalities were seen in six females. One patient with PAN showed renal vasculitis and membranoproliferative glomerulonephritis (MPGN) and was HBV and ANA positive. The patient had negative HCV and cryoglobulins. Five patients with ECV-associated HCV had findings; one had chronic interstitial nephritis and was HBV positive. The other four were HBV negative with MPGN in two, focal proliferative and crescentic GN in one patient each.
CONCLUSIONS:
Increased understanding of the manifestations of systemic vasculitis is likely to provide the basis for the use of more selective immunomodulatory therapies in the future. It is our hope that this study will raise awareness of the non ANCA-associated vasculitic renal involvement

Abstract
BACKGROUND:
Vascular calcification has detrimental consequences on chronic kidney disease (CKD) patients, yet its pathogenesis is not fully understood. Fibroblast growth factor-23 (FGF-23) is involved in the regulation of mineral metabolism which may in turn affect vascular calcification. Data on the relationship between FGF-23 and peripheral vascular calcification, using conventional radiographs, are conflicting, and less is known about its relation to aortic calcification. We conducted this study to investigate the relationship between FGF-23 and aortic calcification in a standard haemodialysis setting.
METHODS:
The study included 65 haemodialysis patients (46 prevalent and 19 incident) on a three times 4-h dialysis schedule as well as 15 controls. Those with diabetes, oral anticoagulation or parathyroidectomy were excluded. Intact FGF-23, parathormone, lipids, calcium and phosphorus were measured. Aortic calcification index (ACI) was assessed by a non-contrast computerized tomography (CT) of the abdominal aorta.
RESULTS:
FGF-23 levels were higher among haemodialysis patients (4681.3 +/- 3906.1 pg/mL) compared to controls (98.2 +/- 51.9 pg/mL), P = 0.005. ACI was higher in haemodialysis patients (14.1 +/- 12) than controls (3.2 +/- 3.6), P = 0.009. FGF-23 (P < 0.0001) and systolic blood pressure (BP) (P < 0.0001) were independently related to ACI in stepwise multiple regression analysis of pooled analysis of haemodialysis patients, R(2) = 0.476; in subgroup analysis, the independent factors relating to ACI among prevalent dialysis patients were systolic BP (P < 0.0001), FGF-23 (P = 0.002) and age (P = 0.012), R(2)=0.48; whereas in incident patients, only FGF-23 was associated with ACI (P = 0.007), R(2) = 0.37.
CONCLUSIONS:
In haemodialysis patients, FGF-23 and ACI were significantly increased, and FGF-23 was independently associated with aortic calcification.

Background: Diabetic nephropathy is a serious complication in individuals with type II diabetes. Infiltration of renal tissue with monocytes secondary to activation by chemokines & their receptors have been implicated in the development of diabetic nephropathy. CCR5 is a chemokine whose signals may mediate monocyte infiltration, differentiation and activation in renal tissue.
Aims: The aim of this work is to determine the relative frequency of chemokine receptor CCR5 G59029A gene polymorphisms in Egyptian patients with type II diabetes and to investigate the possible association of these polymorphisms with diabetic nephropathy.
Methods: This study was conducted on 55 patients with type II DM of duration between 10-20 years. This included 15 patients with no evidence of diabetic nephropathy and 40 patients with diabetic nephropathy, including 30 patients with stage 3-4 chronic kidney disease and 10 with stage 5 chronic kidney disease. CCR5 59029 genotyping was performed using PCR followed by digestion with Bsp1286I restriction enzyme.
Results: We found that the genotype polymorphism frequency in the control group (diabetics without nephropathy) was as follows: GG in 3 out of 15 patients (20%), GA in 3 (20%) and AA in 9 patients (60%). In the pooled analysis of all patients with diabetic nephropathy, the genotype frequency was: GG in 11 out of 40 patients (27.5%), GA in 16 (40%) and AA in 13 (32.5%). The difference in frequencies between controls and nephropathic groups was not statistically significant, p=0.168. There was a trend towards an association between G+ve genotypes (GG and GA) in patients with diabetic nephropathy (67.5%) compared to controls (40%), odds ratio 3.1, p=0.06.
Conclusion: There is a trend towards a possible association between CCR5 G59029A gene polymorphisms and the development of diabetic nephropathy.
Keywords: chemokine receptor 5 (CCR5), type II diabetes, diabetic nephropathy, gene polymorphism

NTRODUCTION AND AIMS: Exposure to lead (Pb) has been a global health problem for decades. Renal effects of acute exposure to Pb as well as chronic high-level occupational exposure are well established. Controversy exists as to the role of low-level environmental exposure to Pb on the kidneys. Body-lead burden (BLB), is known to be elevated among renal failure patients and several explanations were proposed for this, though none is fully confirmed or uniformly accepted. These include: inadequate Pb excretion by the failing kidneys; cause-effect relation between Pb-exposure and renal failure of unknown cause; and an association with hypertension/hypertensive nephrosclerosis. A further proposed possibility is that increased bone-turnover due to 2ry hyperparathyroidism, in renal failure, releases Pb from its dormant stores in bone. We tried to test these various hypotheses head-on, for the first time, in this study

METHODS: We included 84 subjects divided to 2 main groups.Group1: 50 with pre-ESRD (CKD2-4) divided into 3 subgroups: 1a:19 with CKD of known cause; 1b:15 with hypertensive nephrosclerosis; 1c:16 with CKD of unknown cause. Group2: 34 matched controls with normal kidney functions including 18 normtensive and 16 with essential hypertension

All subjects were evaluated by inquiry about sources of environmental exposure to Pb, symptoms/signs suggestive of Pb toxicity, assessment of BLB by EDTA lead-mobilisation test, measurement of serum parathormone (PTH), calcium, phosphorus, alkaline phosphatase, urea, creatinine, uric acid.

Those with occupational exposure to Pb, acute renal failure, malignant hypertension or renal replacement therapy were excluded

RESULTS: 34 CKD patients (68%) vs 1 control (2%) had a positive Pb mobilisation test (>600ug).Only 9 recalled a source of exposure to Pb, those had higher BLB (p0.038) and 3 had symptoms suggestive of Pb toxicity

BLB was higher in CKD patients compared to controls (<0.0001), there was no difference in BLB between different subgroups of CKD patients nor between normo- and hyper-tensive controls. PTH was higher among CKD patients than controls (p 0.001) with no differences between CKD subgroups. PTH was higher in hyper- than normo-tensive controls (p 0.012)

In CKD patients, BLB correlated positively with serum PTH (r 0.7, p 0.0001). This was true for all subgroups (1a: r 0.84, p <0.0001; 1b: r 0.56, p 0.04; 1c: r 0.7, p 0.02). Regarding the other studied parameters, BLB only correlated posititively with serum creatinine (r 0.4, p .007).

In controls, BLB did not correlate with any studied parameter

CONCLUSIONS: We conclude that: a)BLB is elevated in CKD irrespective of the cause of renal failure b)BLB in CKD is related to hyperparathyroidism c) Higher serum creatinine was associated with higher BLB (ie more Pb excretion in urine) (probably due to higher PTH) d) absence of symptoms of Pb toxicity or failure to recall exposure to Pb donot exclude elevated BLB in renal patients.

These results support the hypothesis that elevated PTH releases Pb from its bone stores which may explain several manifestations of and modify treatment for hyperparathyroidism and the uremic syndrome