Rejection of renal allograft. New concepts

Hippokratia 2000, 4 (2): 51-65

G Vergoulas

Abstract

Renal allograft rejection is the sum of a series of immunologic events which cause graft tissue damage and graft failure. During last years, it has been shown that acute allograft rejection is caused by specific alloantigen recognition (HLA -A, -B, -DR) and non-specific inflammation caused by kidney tissue damage during transplantation. Renal allograft rejection can be discriminated into: a) hyperacute rejection that takes place minutes or hours after transplantation and is due to specific preformed anti-HLA Class I and/or anti-ABO antibodies of the recipient against the donor antigens, b) accelerated acute rejection that takes place in a few days after renal transplantation and is due to recipient presensitization against the donor antigens, c) acute rejection that happens 30% of the recipient, days or months after transplantation and d) chronic allograft nephropathy, characterized by non-reversible and inexorable fall of graft function at least three months after transplantation, accompanied by hypertension and proteinuria. This kind of rejection causes graft loss after a few months or years. The main histopathologic finding of chronic allograft nephropathy is intima hyperplasia of the vessel wall combined with glomerulosclerosis or transplant glomerulopathy and interstitial fibrosis or tubular atrophy. The factors that cause chronic allograft nephropathy are of immunologic and non-immunologic origin. Immunologic factors are acute rejection episodes, histocompatibility, previous sensitization, delayed graft function and non compliance with immunosuppressive therapy.Non-immunologic factors are the number of nephrons per kidney (donor/recipient size matching), arterial hypertension, dislipidemia and donor age.There is no hyperacute rejection therapy. Grafts with accelerated acute rejection episode have no long term survival. Corticosteroids and antilymphocyte antibodies are the drugs for antirejection therapy. In patients with chronic allograft nephropathy blood pressure control and dislipidemia therapy are necessary.

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Evaluation of Losartan in patients with renal transplantation

Hippokratia 2000, 4(2):67-72

G Vergoulas, Gr. Miserlis, G. Trellopoulos, A. Antoniadis

Abstract

Arterial hypertension is a major risk factor for cardiovascular morbidity and mortality in renal transplant recipients. Cyclosporine and FK-506 contribute on the development of hypertension. Losartan, a blocker of angiotensin II receptors (ATI), has been proved to be an effective antihypertensive agent. The present retrospective study evaluated the efficacy and safety of losartan in a group of hypertensive patients with normal graft function. Nineteen patients on therapy with antihypertensive drugs were included in the study because of bad blood pressure control and / or drug side effects. These patients (14 men) received losartan 2.9 years after transplantation at the dose of 25-100 mg/d. All patients of the study had serum creatinine levels ≤1.5 mg/dl before treatment with losartan and a twelve month follow up. Systolic (SBP) and diastolic (DBP) blood pressure, serum creatinine (Scr), Ht and Hb were recorded every two months for a period of six months before (BLT) and after initiation of losartan treatment (ALT). Proteinuria and number of antihypertensive agents were recorded BLT (time 0) and six months later. ANOVA for repeated measures, regression analysis for curve estimation and paired t test were used for statistical analysis (SPSS for windows version 9.0).SBP/DBP were 140.71±13.28/86.42±15.34 mmHg, 140.35±13.93/ 90.00±9.60 mmHg, 137.85 ±13.82/91.42±8.86 mmHg, 139.28±13.98/91.07±9.84 mmHg 6, 4, 2 and 0 months BLT respectively (p=NS) and 137.10±8.38/ 85.26±6.55 mmHg, 139.73±13.48/88.15±7.49 mmHg and 142.10±14.65/88.68±7.60 mmHg 2, 4 and 6 months ALT respectively (p=NS). The number of antihypertensive agents per patient was 2.05±0.70/l.68±0.74 (p=0.015), proteinuria was 0.65±0.28/0.52±0.37 g/24h (p=NS) and losartan dose was 50.00±14.43/61.84±24.10 mg/d (p=NS) at time 0 and six months ALT respectively. Scr was 1.14±0.27 mg/dl, 1.17±0.31 mg/dl, 1.20±0.34 mg/dl and 1.12±0.25 mg/dl 6, 4, 2 and 0 months BLT respectively (p=NS, Scr slope =0.00) and 1.18±0.25 mg/dl, 1.21±0.24 mg/dl and 1.23±0.25 mg/dl 2, 4 and 6 months ALT initiation respectively (p=0.038, Scr slope =+0.02). Ht/Hb were 45.94±5.21 %/l4.4±2.06 g/dl, 46.15±5.24% /14.99±1.68 g/dl, 46.20±5.91%/14.98±1.90 g/dl, 46.70±5.42%/15.27±1.74 g/dl 6, 4, 2 and 0 months BLT respectively (p=NS) and 44.28+5.30%/14.26+2.01g/dl,42.83±6.10%/13.98±1.90g/dl,42.24±6.26%/13.81±1.98 g/dl at 2, 4 and 6 months ALT initiation respectively (p=0.02/0.008 respectively). These results show that losartan controls efficiently the blood pressure of hypertensive renal transplant recipients, lowers significantly the need for other antihypertensive agents, causes a significant fall of Ht/Hb and a small but significant rise of serum creatinine level.

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Serum erythropoietin levels of haemodialyzed patients and the necessity for the use of recombinant human erythropoeitin. A Multicenter study

Hippokratia 2000, 4(2):73-78

T. Tsitsios, N. Sotirakopoulos, S. Spaia, V. Derveniotis, C. Chatzidimitriou, K. Mavromatidis

Abstract

The aim of this study was to evaluate the percentage of patients undergoing hemodialysis who do not need rHuEpo, and their haematocrit levels are near the target of DOQIs (Disease Outcomes Quality Initiative). We have registered all the patients undergoing hemodialysis and those with polycystic kidney disease (PKD). Twenty three patients out of 227 (9.8%) did not need rHuEpo and these constituted group A. These patients were evaluated for hepatitis Β virus surface antigen, hepatitis C antigen, the levels of haematocrit, haemoglobin and serum Epo. As a control group we investigated 17 hemodialyzed patients (group B), who had taken rHuEpo. Thirteen patients of group A and 8 of group Β had PDK as cause of renal failure.Patients of group A were statistically significantly older than those of group Β (p<0.03), but they did not show any difference in duration of haemodialysis (p=NS). Haematocrit levels in patients of group A were significantly higher than those of group Β (p<0.001), as well as levels of haemoglobin (p<0.0001) and serum Epo.When we divided each group of patients (A and B) into two subgroups, according to the cause of renal failure (PKD or other non cystic renal diseases), we did not find any difference in haematocrit, haemoglobin and Epo levels.We conclude that: a) 10% of patients undergoing hemodialysis have very good levels of haemoglobin and haematocrit and they do not need rHuEpo, b) serum levels of Epo in these patients are higher than the levels of Epo of patients who need rHuEpo to keep their haematocrit at good levels and c) PDK is not the predominant cause of end stage renal failure in patients who do not need rHuEpo.

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Appendectomy in children

Hippokratia 2000, 4(2):79-84

B. Kasselas, B. Lambropoulos, Ch. Chaidos, Ch. Kasselas, M. Papoutsakis, S. Gavopoulos, N. Nikandrou, G. Grigoriadis

Abstract

Acute appendicitis is the most frequent surgical problem that occurs in childhood. The purpose of our study is to describe the characteristics of acute appendicitis in children, to discuss difficulties of diagnosis and treatment, as well as to compare our findings to those of current literature.In a period of 10 years (1990-1999) 4168 children were operated in our department with a diagnosis of an acute appendicitis. The children were from 2 to 14 years of age and 2834 (68%) of them were boys while 1334 (32%) girls. Blood tests, urinalysis, plain film of abdomen were taken in all cases. Moreover, biochemical tests, x-ray of the chest as well as ultrasound examination and CT of the abdomen were done in neglected or contradictory cases. All the vermiform appendices were histologically examined. 12% (500) of the appendices had no evidence of inflammation, 73% (3043) showed findings of acute appendicitis and 25% (625 were perforated) showed findings of perforation and peritonitis. Leucocytosis was found in 70% of the patients whithout acute appendicitis, in 72% of the patients with acute appendicitis and in 93% of those who had perforation and peritonitis. Peritoneal lavage, placement of drains, starting of feeding, administration of antibiotics, complications and the duration of the hospital treatment depended on the surgical findings. The average length of hospital stay was 4 days for cases with acute appendicitis and 8 days for those with peritonitis.Despite recent advances in laboratory investigation and screening tests the diagnosis of acute appendicitis in children is still difficult and is mainly based on history and physical examination. We expect our conclusions to be useful to physicians who are confronted with such problems in children.

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The gene expression of autosomal dominant polycystic kidney disease (ADPKD). Is there any difference within families?

Hippokratia 2000, 4(2):85-89

D. Tsitsios, N. Sotirakopoulos, M. Mouratidou, S. Papanastasiou, K. Mavromatidis

Abstract
Polycystic kidney disease is caused by mutation in more than two genes and is characterized by an autosomal dominant transmission. It is known that the age at which the onset of end stage renal disease appears is more homogeneous within families than between families. We studied 102 genetic trees with ADPKD, and we found that in four families, 15 patients suffered from the disease, four women (one from each family) had a different renal expression of their abnormal gene. Especially one woman in each of the above four families continued to have normal renal function while the other members of the same family had end stage renal disease or severe renal failure. It is emphasized that there were no any differences between the members of the same family, regarding the existence of hypertension or their protein diet e.t.c, that in turn could influence their renal function. So we concluded that patients with ADPKD from the same family could have different renal expression of their abnormal gene.

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Loin pain-hematuria syndrome. Report of 2 cases

Hippokratia 2000, 4(2):90-93

N. Sikas, A. Asderakis, H. Riad

Abstract

Loin pain-hematuria syndro-me is a rare disease, of unknown etiology, characterized by severe loin pain, persistent hematuria and normal kidney function. In this study 2 cases are reported and the diagnostic and therapeutic approach are analyzed.Two patients (1 female and 1 male, aged 38 and 32 years respectively) presented with progressively deteriorating loin pain (bilaterally the 1st patient and on the left side the second one) and hematuria for 4 and 6 years respectively.
During this period of time they underwent detailed radiological investigations including intravenous pyelography, CT scan and renal angiogram as well as renal biopsy and full immunological, hematology and biochemistry tests. All these tests were found to be normal and for the pain control they were on non-steroidal anti-inflammatory drugs and high doses of opioids. Both of them underwent autotransplantation, bilateral the 1st patient and on the left the 2nd patient.
The 1st patient developed recurrent symptoms on the right side 14 years after autotransplantation. This was initially managed with sympathectomy and 3 years later she required nephrectomy because of persistent symptoms. The 2nd patient, 12 months after his autotransplantation remains asymptomatic and takes no analgesia.Autotransplantation is the only way of managing the symptoms of this syndrome. In case of recurrence, nephrectomy is considered absolutely necessary.

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