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The aim of this study was to evaluate the activity of rheumatoid arthritis (RA) by hand radiography (Sharp's radiographic index), and assessment of acute phase reactants - erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF), and to determine their value as prognostic markers for disease outcome in patients with early RA treated with disease modifying antirheumatic drugs (DMARDs)-Methotrexate (MTH); to register and quantify clinical, radiographic and laboratorial differences in certain time intervals in a group of patients treated with immunomodulation therapy with MTH; to determine which of the acute phase reactants would be the most useful marker for evaluation of disease activity in long-term follow-up in RA patients; to select high-risk groups with aggressive course of disease, in order to emphasize the necessity of early and aggressive treatment. Thirty patients with early RA (disease evolution up to 1 year) were evaluated in several time intervals. The score of the Sharp's index showed greater radiographic progression of the joint damage of hands in time intervals between 0-time and 12 months (p=0.0167) and between 0-time and 18 months (p=0.0089). Statistical analysis showed differences in values of CRP in four time intervals (p=0.00002). Considering CRP, there were statistically significant differences among mean values in four time intervals (p=0.0428) (standard deviations showed greater variations). There were no statistically significant differences among mean values of RF in four time intervals (p=0.573). At 0-time in 3 (10%) patients progression of the Sharp's index was found, after 6 months in 13 (39%) patients, while after 12 and 18 months progression of the Sharp's index was found in an identical number of patients, 15 (50%). In most patients high values of CRP and RF were found. Progression of the radiographic damage is especially expressed in patients with high values of ESR, CRP, RF and existence of previous erosions of hands, which are predictors for aggressive course of disease. CRP is the most useful marker for the evaluation of RA activity in the long-term follow-up of RA patients.

The fast development of nephrology in the world, especially in the second half of the 20 th century demanded protocol (guidelines) for nephrological activity for all levels of medical care, of doctors and specialists. The International Society of Nephrology, the European Renal Association and other national associations created their own protocol (guidelines) for nephrological activity. The Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial Organs (MSNDTAO) proclaimed the First Protocol for Performing Nephrological Activity in the Republic of Macedonia at the First Congress of the MSNDTAO, held in Ohrid 1993, and it was published in the Macedonian Medical Review, 1994; Supplement 14: 397-406 [1]. The update of the Protocol for Performing Nephrological Activity in the Republic of Macedonia was proclaimed at the Fourth Congress of MSNDTAO, held in Ohrid 2012 and it presented in this text.

Aim: To determine differences between groups with hypertension in pregnancy and assess risk factors associated with preeclampsia., Patients and Methods: In the period 2008-10 at the Department of Nephrology in Skopje, Macedonia, a prospective and a longitudinal study study comprising 134 pregnant women was carried out. They had regular monthly check-ups in pregnancy and after delivery (1-8), when groups were defined as gestational hypertension, pre-existing hypertension, superimposed preeclampsia, and preeclampsia. A total of 134 women were regularly controlled by 24-hour ambulatory monitoring of blood pressure (24ABPM), blood and urine, D-dimers, and a resistance index of the Doppler of the umbilical artery (RI a.umb), and a questionnaire on risk factors was filled in for every pregnant woman., Results: Superimposed preeclampsia was found in 22 (16.4%) and preeclampsia was found in 20 women (14.9%). Daily diastolic blood pressure of 24-hour blood pressure monitoring at the last check-up before delivery was significantly higher in the group with superimposed preeclampsia (SP) 87.6±9.5 and in the group with preeclampsia (PE) 87.9±7.7 mm Hg. Previous preeclampsia (OR=3.28), primiparity (OR=2.35), methyldopa (OR=3.76), number of check-ups (OR=2.3), positive family history (OR=1.4) and in vitro fertilisation (OR=1.15) were found as risk factors associated with the occurrence of preeclampsia and preeclampsia superimposed on preexisting hypertension., Conclusions: Early determination of risk factors should prompt more frequent check-ups in hypertensive pregnancies in order to determine timely delivery and avoid adverse outcomes in the mother and child.

Aim: to determine differences in regulation of blood pressure and renal function in patients with moderate intake of alcohol (1-14 units per week)., Material and Methods: Cross-section study performed at the Department of Nephrology. Seventy-six patients admitted for diagnosis and treatment of hypertension were included. Patients with diabetes mellitus, renal failure and other coorbidities were excluded from the study. Medical history, data on alcohol consumption, laboratory analysis, Doppler echosonography of intrarenal blood vessels and 24-hour blood pressure monitoring were performed. The group that consumed alcohol (A+) consisted of 10 patients, while the group that did not (A-) consisted of 66 patients. The two groups were comparable by age, BMI and hypertension history. Two groups were compared by the values of their blood pressure, BMI, hypertension history in months, serum creatinine, uric acid, Doppler duplex index of renal resistence, triglycerides and cholesterol., Results: In group A+ , the serum creatinine was significantly higher, but still within the normal range (86.3+/-15.72 vs 71.75+/-14.77, p=0.005). Serum uric acid followed the same trend (360.3+/-110.18 vs. 284.4+/-95.28, p=0.026. Pulse pressure and mean arterial pressure were higher in the A+ group (71.33+/-19.23 vs. 57.65+/-16.78, p=0.028 and 127.81+/-17.6 vs 111.02+/-21.67, p=0.03 respectively). Serum lipids were unsignificantly higher in the A+ group (9.56+/-1.5 vs 9.02+/-1.59, p=0.38). No changes between groups were registered with Doppler sonography of intrarenal blood vessels. In women, consumption of alcohol was associated with blood pressure control., Conclusion: Moderate alcohol consumption is associated with the regulation of the blood pressure.

Aim: To determine the concentrations of nitric oxide (NO) in plasma of women with essential hypertension in prehypertensive phase, its effect on blood pressure, and correlation with other vasoactive substances that regulate systemic and renal vascular tonus., Methods: The study performed at the Department of Nephrology, Hospital Center in Skopje, Macedonia, included 26 women with essential hypertension in prehypertensive phase and 11 normotensive women as healthy controls. Vasodilating factors NO and 6-keto-prostaglandin F1 alpha (6-keto-PGF1alpha) were determined in plasma. Thromboxane B2 (TXB2) as a vasoconstricting factor and electrolytes Na+, K+, and Ca2+ were determined in urine. Blood pressure was monitored over 24 hours. Systolic, diastolic, mean blood pressure were presented as average 24-hour values., Results: The concentrations of NO and 6-keto-PGF1alpha were significantly lower in women with essential hypertension in prehypertensive phase than in their normotensive controls (NO: median 22, range 11-35 vs median 37.5, range 11-66; 6-keto-PGF1alpha: 64.8+/-14.35 vs 98.21+/-43.45 micromol/L; P<0.001). The index of vascular reactivity (TXB2/6-keto-PGF1alpha ratio) was higher in women in prehypertensive phase than in normotensive women (1.3 vs 0.8, P<0.001). Urinary calcium to creatinine ratio was significantly lower in the prehypertensive group (0.06+/-0.03 vs 0.24+/-0.13, P<0.001). No direct correlations were found between NO, TXB2, and 6-keto-PGF1alpha, or between NO and electrolytes in the urine. Low NO and urinary Ca2+ were significant indicators of increased blood pressure (P=0.013 and P=0.024, respectively; backward stepwise multiple regression analysis)., Conclusions: NO and 6-keto-PGF1alpha were significantly lower in women in prehypertensive phase of essential hypertension. Lower NO correlated with increased systolic blood pressure, but not with on natriuresis and calciuresis. These findings, together with the higher vascular reactivity index, indicate that endothelial dysfunction precedes the establishment of essential hypertension.

A number of laboratory tests are available for evaluation of hypertension in pregnancy. These tests can be used to either predict and/or prognosticate preeclampsia and other hypertensive disorders of pregnancy. The aim of this study was to evaluate alterations in fibronectin homeostasis in normotensive pregnancy and in hypertensive disorders of pregnancy subclassified into chronic hypertension, preeclampsia superimposed on chronic hypertension, and pregnancy induced hypertension. A prospective, longitudinal study was conducted in 115 pregnant women aged 20-39 years, divided into four groups: normotensive (n = 40), chronic hypertension (n = 18), preeclampsia superimposed on chronic hypertension (n = 20), and pregnancy induced hypertension (n = 37). Plasma concentrations of fibronectin were measured by using single radial immunodiffusion assay (RIA) in the 8th, 18th, 23rd, 28th, 32nd and 36th week of gestation. Plasma fibronectin concentration showed no significant changes in normotensive pregnancy, but was significantly elevated in the third trimester in women destined to become preeclamptic or with preeclampsia in whom it reached a mean (+/- SD) of 0.40 +/- 0.09 g/L in the 36th week of gestation. In the groups with preeclampsia superimposed on chronic hypertension and with pregnancy induced hypertension, there was a significant difference between plasma fibronectin concentrations in 32nd (p < 0.01) and 36th (p < 0.001) week of gestation compared with either other levels in the respective group (in the 8th, 18th, 23rd and 28th week of gestation) or those recorded in other groups in the same period of pregnancy. These results suggested that the measurement of plasma fibronectin might be of diagnostic value in preeclampsia but could not be considered a useful predictor for preeclampsia.

In 24 young normotensive subjects (mean age 22.25 +/- 5.65 years) with one hypertensive parent (FH(+)-), 22 subjects (mean age 23.55 +/- 5.17 years) with two hypertensive parents (FH+ +/-), and a control group of 16 age and gender matched subjects (mean age 22.50 +/- 6.00 years) with two normotensive parents (FH--), creatinine clearances and microalbuminuria (MA) were measured. Blood pressure was monitored for 24 hours and mean arterial pressure (MAP) was calculated and compared between groups. No significant differences were recorded. FH(+)- and FH++ subjects had significantly higher MAP over the sleeping period than FH-- subjects (78.63 +/- 1.71, 78.95 +/- 1.27; and 72.91 +/- 1.35 mmHg respectively; p < 0.02). Creatinine clearance was higher in FH(+)- and FH++ group compared to FH-- subjects (2.39 +/- 0.17; 2.29 +/- 0.17; and 1.66 +/- 0.11 ml/sec respectively; p < 0.01). Hyperfiltration correlated with MAP in FH++ subjects (2.29 +/- 0.17 ml/sec; 92.45 +/- 7.39 mmHg; r = 0.52 i p < 0.03). MA correlated neither with creatinine clearance nor with MAP. Our results suggest that hypertension may develop as a consequence of the long-lasting, higher GFR, which may accelerate the age-related process of sclerosis both in the small arterioles and the glomeruli.

In 48 men, 42, 1 +/- 8.8 yrs old, with untreated mild essential hypertension, serum uric acid, total cholesterol triglycerides and glucose were examined at 8 a.m after 16 hour overnight fasting. All patients were overweight, with body mass index: 26.9 +/- 2.4 kg/m2, (normal value: 19-24.9); serum uric acid 293.1 +/- 89.3 mmol/l; cholesterol 6.3 +/- 1.4; triglycerides 2.0 +/- 1.3 and glucose 5.4 +/- 0.9 mmol/l. File out of 48 (10.4%) patients had hyperuricemia, nine (18.7%) had hypercholesterolemia, twenty (41.7%) had hypertriglyceridemia and 19 (39.6%) had hyperglycemia. Significant correlation between serum uric acid and triglycerides only (r = 0.35; p < 0.01), was found. A correlation exists between the diastolic blood pressure and cholesterol (r = 0.35; p < 0.01); as well as, between mean arterial blood pressure and cholesterol (r = 0.34; p < 0.02). Only three out of 48 (6.2%) patients with hypertension had all four biochemical parameters above normal levels. Our results suggest that interrelation of all these metabolic disorders are important in essential hypertension, and especially the association of high serum uric acid and triglyceride level.

We present a case of an extremely rare form of Ewing sarcoma--primary disseminated, with fulminating course, severe hypercalcemia, extensive calcium deposition in parenchymatous organs, including kidneys, and acute renal failure as a clinical consequence. Correction of hypercalcemia was followed by prompt restoration of the glomerular filtration rate (GFR), suggesting that hypercalcemia had a direct effect on its regulation independent of the renal tubular damage. The effectiveness of the treatment with indomethacin indirectly supports the possibility of prostaglandin-mediated humoral hypercalcemia of malignancy.

Ten patients, mean age 51.50 +/- 3.03 years, with degenerative rheumatism on NSAID treatment without any sign of renal disease, and 11 control subjects, mean age 43.50 +/- 1.51 years, were studied. NSAID treatment was of 11.30 +/- 5.60 weeks duration in average, with ibuprofen, naproxen, or indomethacin. Urinary excretion of three specific renal tubular enzymes--AAP: alanine-amino-peptidase, GGT: gamma-glutamyl-transpeptidase, and beta-NAG: beta-N-acetyl-glucosaminidase, were determined in 8-h overnight urine samples, as well as GFR creatinine clearance/1.73 m2, urinary volume/8 h, specific gravity of the urine, proteinuria and glucosuria. In the group treated with NSAIDs, urinary excretion of the enzymes was significantly higher than in the control group--AAP: 1414.20 +/- 317.60, 864.20 +/- 94.42, p < 0.00001; GGT: 8034.6 +/- 1378.55, 5095.64 +/- 614.40, p < 0.00001, and beta-NAG: 1644.60 +/- 299.97, 964.82 +/- 142.00, p < 0.00001. Patients on NSAID treatment showed abnormal urinary excretion of AAP in 7/10 cases, of GGT in 6/10, and of beta-NAG in 7/10 cases. Duration of the treatment did not correlate with the urinary excretion of the enzymes. Age was in correlation with the urinary excretion of the enzymes only in the control group, r = 0.52, p < 0.005 for AAP, r = -0.43, p < 0.02 for GGT, and r = -0.23, p < 0.05 for beta-NAG.(ABSTRACT TRUNCATED AT 250 WORDS)