Chronic kidney disease progression in native and transplant kidneys

PURPOSE OF REVIEW: The present review addresses the recent literature demonstrating important differences in the rate of progression of kidney function decline between transplant recipients and patients with native kidney disease. It also highlights the need for prospective studies to determine the importance of nonimmune factors that are established risk factors for progression of native kidney disease in the transplant setting. RECENT FINDINGS: Transplant recipients establish modest levels of kidney function but have rates of kidney function decline that are slower than those in patients with native kidney disease. Continued improvements in long-term graft survival have not been achieved despite significant advances in immunosuppression. There is increasing observational evidence that nonimmune factors that play a causal role in progression of native kidney disease may also be important determinants of allograft decline. There are fundamental differences between transplant recipients and patients with native kidney disease that preclude extrapolation of evidence from native kidney disease to the transplant setting. SUMMARY: Transplant recipients are a unique group of chronic kidney disease patients. Prospective studies to determine the importance of nonimmune factors such as hypertension, proteinuria, dyslipidemia, diabetes, and anemia in the transplant setting are needed.     

Chronic kidney disease progression in kidney transplant recipients: A focus on traditional risk factors

Kidney transplant recipients are a subset of patients with chronic kidney disease (CKD) that remain at high risk for progression to dialysis and mortality. Recent advances in immunosuppression have only partially improved long‐term graft and patient survival. Discovery of new immunosuppressive regimens is a slow and resource‐intensive process. Hence, recognition and management of modifiable allogeneic and non‐allogeneic risk factors for progression to CKD among kidney transplant recipients is of major interest for improving long‐term outcomes. Graft survival is mainly determined by the quality of the allograft and by the patient’s alloimmune response, which is influenced by human leukocyte antigen matching and the presence of donor‐specific antibodies. Alloimmune responses manifest as acute and chronic forms of cell‐ and antibody‐mediated rejection, which can be worsened by patient non‐adherence or under‐immunosuppression. However, donor and patient ages, glomerular disease recurrence, time on dialysis, pre‐existing cardiovascular burden, medication side‐effects and traditional risk factors, such as hypertension, proteinuria, anaemia, dyslipidaemia, diabetes and bone mineral disorder, which can ultimately lead to severe endothelial derangement, also contribute to graft loss and mortality. These traditional risk factors, common to pre‐dialysis patients, often are considered of secondary importance when compared to alloimmunity and immunosuppression concerns. In this review article, we focus on the epidemiological, pathophysiological and therapeutic features of non‐allogeneic traditional risk factors for CKD. We also discuss the benefit of adopting a multidisciplinary approach to pursue the same therapeutic targets recommended for pre‐dialysis patients.     

Chronic kidney disease increases risk for venous thromboembolism

Chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease morbidity and mortality, but its association with incident venous thromboembolism (VTE) in non-dialysis-dependent patients has not been evaluated in a community-based population. With the use of data from the Longitudinal Investigation of Thromboembolism Etiology (LITE) study, 19,073 middle-aged and elderly adults were categorized on the basis of estimated GFR, and cystatin C (available in 4734 participants) was divided into quintiles. During a mean follow-up time of 11.8 yr, 413 participants developed VTE. Compared with participants with normal kidney function, relative risk for VTE was 1.28 (95% confidence interval [CI] 1.02 to 1.59) for those with mildly decreased kidney function and 2.09 (95% CI 1.47 to 2.96) for those with stage 3/4 CKD, when adjusted for age, gender, race, and center. After additional adjustment for cardiovascular disease risk factors, an increased risk for VTE was still observed in participants with stage 3/4 CKD, with a multivariable adjusted relative risk of 1.71 (95% CI 1.18 to 2.49). There was no significant association between cystatin C and VTE. In conclusion, middle-aged and elderly patients with CKD (stages 3 through 4) are at increased risk for incident VTE, suggesting that VTE prophylaxis may be particularly important in this population.     

Posttraumatic syringomyelia: predisposing factors

Posttraumatic spinal cord cavitation (syrinx) and progressive myelopathy associated with a posttraumatic syrinx (PTS) have been recognized for many years. Predisposing factors for PTS have not been well defined. All symptomatic PTS patients (n = 58) treated at the University of Toronto neurosurgical units over 30 years were analysed retrospectively to discover risk factors for the development of PTS. There were 46 males and 12 females (mean age 42.2 years); 28 patients had cervical (CSCI), and 30 had thoracic and lumbar spinal cord injuries (TSCI). Neurological deficit was complete in 40 (69%) compared with 43% complete injuries in the concurrent spinal and injury (SCI) population in general (p = 0.0003). Onset of PTS was earlier with: increasing age (p < 0.02), cervical and thoracic levels of injury (p < 0.007 and p < 0.02, respectively, compared with lumbar injuries), dislocated fractures (p < 0.003) and spinal surgery (p < 0.001) and, marginally, with complete SCI (p = 0.06). Mean time to onset of PTS appears to have decreased in recent years (p < 0.0001). PTS follows complete spinal cord injury (SCI) more often than incomplete and is frequently associated with arachnoiditis. Onset is earlier with increasing age, cervical and thoracic levels compared with lumbar, displaced fractures and spinal instrumentation without decompression. A group of SCI patients who are at greater risk of developing early PTS is thus identified, facilitating cost-effective follow-up.     

Renal transplant recipients and chronic liver disease: statistical evaluation of predisposing factors.

278 azathioprine and methylprednisolone (AZA)-treated and 406 ciclosporin (CS) treated patients with a kidney graft functioning for more than 1 year were investigated for the presence of chronic liver disease (CLD), defined as an increase in transaminases of 1.5 times the upper normal limits for a period of at least 12 months. The prevalence of CLD was 36 and 27% in the two groups, respectively. The univariate analysis showed that male sex, alcohol abuse and HBsAg positivity correlated with CLD onset in the AZA group while blood transfusions, length of dialysis treatment, pretransplantation CLD, HBsAg positivity and ferritin levels over 800 ng/ml correlated with CLD onset in CS. The multivariate analysis identified male sex and HBsAg positivity in the AZA group and age over 18 years, high ferritin levels and HBsAg positivity in the CS group as risk factors predictive of CLD onset. Liver failure represented the 4th cause of death in the AZA group but 1 of the 2 most important causes of death in CS in the long term. However, these drawbacks were overcome by the overall low mortality rate in CS. Therefore, renal transplantation should not be refused to patients positive for HBsAg and/or with preexisting liver disease.     

Segmentary venous hypervolemia as one of the main factors of the patho-hemodynamic development and progression of chronic venous insufficiency of lower extremities in patients with varicose disease

Phlebographic examinations carried out in 91 patients with varicosity and 30 healthy subjects have determined structural peculiarities of the intramuscular shin veins in health and disease. A comparison of the anatomical findings with the degree of hemodynamic abnormalities allowed to make a conclusion that intramuscular segmental hypervolemia should be considered as one of the main pathogenic links in the pathophysiological chain of the development of chronic venous insufficiency. Further elevation of supravalvate venous segmental actazia forms a relative valve incompetence at the particular level which promotes the spreading of retrograde pathological blood flow in distal direction. Blood shunting into the intramuscular shin veins is one of the compensatory mechanisms of increasing pathological hypervolemia as a cause of valve incompetence and retrograde blood flow. The procedure of evacuation from the skin veins directly depends on the effective work of the shin muscular-venous pump. Further involvement of the intramuscular veins in the pathological process, the low effectiveness of the shin muscular-venous pump results in greater dysfunction and finally forms a hypodynamic vicious circle of chronic venous insufficiency with all its manifestations.     

Chronic venous insufficiency

Like the noninvasive assessment of arterial occlusive disease, the various methods for evaluation of chronic venous insufficiency (CVI) can be divided into those that provide hemodynamic information and those that provide anatomic detail. The majority of noninvasive methods for evaluation of CVI are directed toward assessing hemodynamic events in large vessels by detecting abnormally directed blood flow, elevated venous pressure, increased limb-volume changes, or valvular reflux. B-mode ultrasound, the principal non-invasive method for anatomic assessment of CVI, defines either valvular incompetence, obstruction, or recanalization changes.     

Chronic venous disease treated by ultrasound guided foam sclerotherapy.

AIM: To report the outcome of a series of patients with chronic venous disease due to incompetence of saphenous trunks managed by ultrasound guided foam sclerotherapy (UFS). PATIENTS AND METHODS: A group of 808 patients comprise this series. CEAP clinical class for limbs was C1: 15%, C2: 81%, C3: 0.5%, C4: 2%, C5: 0.2%, C6: 0.4%. UFS using 1% polidocanol (107 limbs), 1% sodium tetradecyl (102 limbs), 3% sodium tetradecyl (900 limbs) was employed to treat incompetent saphenous trunks. In patients with unilateral varices 1 treatment was required in 43% of patients and 2 treatments in 48% of patients to obliterate incompetent saphenous trunks and varices. For bilateral varices 2 treatments were required in 40% of patients and 3 treatments in 46% of cases. The clinical outcome and patency of treated veins on duplex ultrasonography was assessed at a mean follow-up interval of 11 months. RESULTS: A total of 459 limbs were available for assessment at a follow-up interval of 6 months or greater. The CEAP clinical stage was C0:182 limbs, C1: 241, C2: 22, C3: 0, C4: 11, C5: 2, C6:1. The GSV had remained obliterated in 88% of limbs and the SSV in 82% of limbs. Recurrent venous incompetence following previous surgery was as effectively treated by UFS as primary incompetence. CONCLUSIONS: This technique is useful in the management of chronic venous disease as an alternative to surgery.     

Frostbite: predisposing factors and predictors of poor outcome

A retrospective review of 79 frostbite cases over a 10-year period at a major Northern Canadian hospital was performed. Factors predisposing to frostbite injury and predictors of a poor outcome were sought. Impaired cerebral function was found to be the major predisposing factor to frostbite injury. At the time of injury, 53% of patients were under the influence of alcohol and 16% were suffering from psychiatric illnesses. Lower extremity frostbite, infection, and delay in seeking medical attention were factors found to be associated with a poor outcome.     

Gallstone pancreatitis. Local predisposing factors.

Local predisposing anatomic and stone factors were studied in 150 patients with gallstones in order to analyze why some patients with cholelithiasis acquire gallstone pancreatitis and others do not. Number and size of gallstones in the gallbladder and common bile duct, presence of pancreatic duct reflux, diameter of the cystic duct, and size of the duodenal orifice and ampulla of Vater were all studied in 75 patients with gallstone pancreatitis (Group I), 75 patients with cholelithiasis (Group II), and by dissections in 50 autopsy specimens. Stones 5 mm or less in diameter were present in 51 (70%) of Group I gallbladders as compared to 30 (41%) of Group II patients (p less than 0.001). Impacted common bile duct stones were found in 21 (29%) of the Group I patients and only four (5%) of the patients in Group II (p less than 0.001). The mean size of the stones that impacted at the ampulla of Vater in the Group I patients were 3.10 mm, whereas in the Group II patients the mean size of the stones was 7.50 mm (p less than 0.001). The Group I cystic ducts were larger (3.80 mm) than the ducts in the Group II patients (2.36 mm) (p less than 0.001). On operative cholangiography, 50 (67%) showed reflux of contrast material into the pancreatic duct compared to only 14 (18%) in the control Group II (p less than 0.001). These data indicate that small gallbladder stones, enlarged cystic ducts, properly sized impacted stones, and a functioning common channel are predisposing local etiologic factors in the development of gallstone pancreatitis.     

Study of the venous reflux progression

BACKGROUND: Patients with chronic venous disease (CVD) often ask whether elective vein surgery could be delayed without consequences. Because the natural history of CVD is not well known, this study was designed to determine its progression in such patients. METHODS: One hundred and sixteen limbs in 90 patients who had at least 2 exams with duplex ultrasound (DU) scanning prior to vein surgery at a university medical center were studied. These were patients who were offered an operation but for various reasons were treated at a later stage. Patients were classified by the CEAP system. RESULTS: The mean age of the patients was 49 years (range, 23 to 81 years). A second DU scan was performed 1 to 43 months after the initial exam (median, 19 months). Eighty-five limbs (73.3%) were unchanged. Thirteen limbs (11.2%) had progression of clinical stage, and seven had progression on DU scanning as well. Seven limbs progressed from C2 to C3, four limbs from C3 to C4, and two limbs from C4 to C6. Thirty-four limbs had a documented change on repeat DU scanning. In 3 of these limbs, reflux was missed on the initial exam; therefore, 31 limbs had progression of disease. The great saphenous vein and tributaries were the most often anatomic sites affected by a change, followed by perforators. Seventeen limbs (14.7%) had extension of pre-existing reflux, and 14 (12.1%) had reflux in a new segment. In 11 of these limbs, a change in the initial plan for treatment was required. Symptomatic or DU changes were noted 6 months or later in 95% of limbs and 74.2% of limbs with disease progression were diagnosed at 12 months or later. All but one of the 13 symptomatic limbs developed symptoms at least a year later. CONCLUSION: Nearly one third of patients with venous reflux had progression. Anatomic extension is frequent with disease progression but not a pre-requisite. Progression was found in most limbs 6 months after the initial study. Patients undergoing treatment for their veins may need another DU exam if this time interval is exceeded.     

Body size and weight as predisposing factors in varicocele

OBJECTIVE: The literature regarding the constitutional type of children and adolescents with varicocele is inconsistent. The aim of this investigation was to examine a possible influence of weight, height and body mass index (BMI) on the formation of varicoceles during childhood and adolescence. MATERIAL AND METHODS: In a retrospective data analysis, 193 Caucasian children and adolescents aged 9-19 years (mean age 14.7 years) with left-sided varicocele grade 2-3 were studied. The weight, height and BMI of the subjects were compared with the age-correlated normal values currently accepted in Germany. Additionally, the familial disposition for varicocele and the occurrence of relevant concurrent diseases were considered. RESULTS: In the group of patients examined, the mean percentiles of weight (57th) and height (58th) were significantly above and the mean BMI percentile (42th) was significantly below the age-correlated 50th percentile for the normal population (p=0.019, 0.005 and 0.002). In our case material, 12.2% of all brothers of the patients had varicoceles. CONCLUSIONS: The results of this investigation suggest a correlation between physical appearance and the formation of a varicocele during childhood or adolescence. We were able to demonstrate that patients with varicocele were heavier and taller than an age-correlated normal population, but had a distinctly lower BMI. Further studies are needed to verify whether this rather athletic habitus, together with the postulated difference in muscle:fat ratio, represents an important etiologic factor for varicocele formation.     

Chronic venous disease in a cohort of healthy UK Asian men.

OBJECTIVES: This group has previously reported that UK Asians are significantly less likely to undergo surgery for lower limb venous disease than age and sex matched Caucasians. The aim of the present study was to estimate the prevalence of lower limb chronic venous disease (CVD) in the UK Asian male population. DESIGN: A prospective, epidemiological survey. MATERIALS AND METHODS: 100 unselected Asian men attending a local Mosque were assessed for the evidence of lower limb CVD, involving the collection of data on history and clinical signs and objective assessments of venous pathophysiology using lower limb venous ultrasonography and venous photoplethysmography (PPG). RESULTS: On clinical examination, 80 limbs (in 50 subjects) had clinical evidence of CVD, the majority of cases consisting of varicose veins (CEAP C2). No limbs had either healed or active ulceration (C5/6), and only 2 limbs had thread veins (C1). Eight subjects had had previous venous surgery. The venous refill time (vRT) measured by PPG was lower in limbs with CVD. On venous ultrasound, reflux was present in 73/200 limbs, affecting primarily the GSV system, with only 7 limbs having deep venous reflux. CONCLUSIONS: Present data strongly suggest that the low rates of superficial venous surgery in UK Asians is not because they are inherently less likely to develop CVD.