Contrast nephropathy

Contrast nephropathy is an adverse alteration in renal function induced by intravascular contrast media. Most cases involve transient asymptomatic episodes; yet a significant number involve oliguria and/or permanent renal damage. The incidence of contrast nephropathy in the general hospitalized population is about 5%, and is associated with preexisting renal insufficiency and diabetes mellitus. The incidence in patients with normal renal function is significantly lower - 0.6% following IVP and 2% following angiography. Angiography carries risks inherent to the technical problems of the procedure itself. Preexisting renal insufficiency is the most significant predisposing condition of contrast nephrotoxicity. As many as two-thirds of patients with chronic renal failure may experience an acute deterioration in renal function following exposure. Most of these episodes are transient and benign. Diabetic patients with preexisting renal insufficiency are at an even greater risk; about 75% of such patients will experience renal complications. The risk is even higher in JODM patients with severe renal disease; there is an over 90% incidence of nephrotoxicity with as many as half sustaining permanent renal damage. Adequate hydration does not appear to reduce the incidence of contrast nephropathy in susceptible patients, but it may reduce the likelihood of oliguria and permanent damage. In multiple myeloma the risk of contrast-induced renal failure is low, and probably involves a different pathogenesis than seen in other cases of contrast nephropathy. The incidence in myeloma patients is probably increased in the presence of dehydration and renal insufficiency. Peripheral vascular disease, hypertension, old age and large and repeated doses of contrast may increase the risk in susceptible patients. Prevention of contrast nephropathy must start with identification of patients at risk. In patients with preexisting renal insufficiency, and especially diabetic patients with preexisting renal insufficiency, the anticipated benefit should outweigh the potential risk of exposure to contrast media.     

Predicting initiation and progression of chronic kidney disease: Developing renal risk scores

Epidemiological studies have raised awareness of the problem of undiagnosed chronic kidney disease (CKD) and suggest that early identification and treatment will reduce the global burden of patients requiring dialysis. This has highlighted the twin problems of how to identify subjects for screening and target intervention to those with CKD most likely to progress to end-stage renal disease. Prospective studies have identified risk factors for CKD in the general population as well as risk factors for progression in patients with established CKD. Risk factors may thus be divided into initiating factors and perpetuating factors, with some overlap between the groups. In this paper, we review current data regarding CKD risk factors and illustrate how each may impact upon the mechanisms underlying CKD progression to accelerate loss of renal function. We propose that these risk factors should be used as a basis for developing a renal risk score, analogous to the Framingham risk score for ischemic heart disease, which will allow accurate determination of renal risk in the general population and among CKD patients.     

Hyperhomocysteinemia, malnutrition, and inflammation in ESRD patients

Hyperhomocysteinemia is a risk factor for cardiovascular disease in the general population, but in end-stage renal disease patients some studies show a reverse association, i.e. higher levels of homocysteine are associated with better clinical outcome. In this brief review, we review the evidence that malnutrition, hypoalbuminemia, inflammation and diabetes mellitus may lower circulating levels of homocysteine. As these factors are strong predictors of clinical outcome, this may explain why lower homocysteine levels in end-stage renal disease patients are associated with worse clinical outcome. We conclude that these factors need to be taken into account in multivariate models evaluating the impact of hyperhomocysteinemia as a risk factor in end-stage renal disease patients.     

Use of renal risk drugs in hospitalized patients with impaired renal function--an underestimated problem?

BACKGROUND: Inappropriate use of drugs in patients with renal impairment (RI) may be harmful and may have deleterious effects. We aimed to investigate the use of renal risk drugs in such patients in general hospitals and to analyse the relationship to demographic factors, risk factors and occurrence of drug-related problems (DRPs). METHODS: Patients admitted to departments of internal medicine and rheumatology in five general hospitals were included. We recorded demographic data, drugs used, drugs described to be a risk in RI (renal risk drugs), relevant medical history, laboratory data and clinical/pharmacological risk factors. We used levels of glomerular filtration rates, calculated by the Modification of Diet in Renal Disease formula to classify patients into five stages of renal function. DRPs were recorded and assessed in multidisciplinary hospital team discussions. RESULTS: Of the 808 included patients, 293 (36%) had normal renal function (stage 1), 314 (39%) had mild RI (stage 2), 160 (20%) had moderate RI (stage 3), 35 (4%) had severe RI (stage 4) and six (0.7%) had kidney failure (stage 5). Mean number of drugs used per patient in patients with RI (stages 3, 4 and 5) and patients evaluated to have adequate renal function relative to drug therapy (stages 1 and 2): on admission 6.2 vs 4.1; started in hospital 4.3 vs 3.9 and total number of renal risk drugs 6.1 vs 4.5. All but six patients with RI stages 3, 4 and 5 used two or more renal risk drugs. 124 (62%) of the patients with RI stages 3, 4 and 5 had DRPs linked to the renal risk drugs, and 26% of the renal risk drugs were associated with DRPs. The most common drug classes associated with DRPs were antibacterials, antithrombotic agents, angiotensin-converting enzyme (ACE) inhibitors, opioids and non-steroidal anti-inflammatory drugs (NSAIDs). CONCLUSIONS: Among patients admitted to general hospitals, a considerable proportion had renal impairment. In patients with reduced renal function, renal risk drugs were widely used and often in combination. DRPs were frequently associated with the use of renal risk drugs.     

The role of the pediatric nephrologist in the care of children with diabetes mellitus

The pediatric nephrologist has traditionally not been involved in the care of the diabetic child since diabetic nephropathy presents in adulthood. Recent studies suggest that diabetic kidney disease develops silently during childhood. Measurement of urinary albumin excretion (UAE) allows earlier detection of patients at risk of nephropathy, often in adolescence. In addition to diabetic nephropathy, diabetic children are at risk of urinary tract infections, renal papillary necrosis, and various forms of glomerulonephritis. The role of the pediatric nephrologist in the care of the child with diabetes might include advising on the administration and interpretation of screening for UAE and the measurement and interpretation of glomerular filtration rate, and blood pressure. Children with evidence of renal dysfunction should be evaluated and treated by the pediatric nephrologist. Frequently, renal biopsy will be necessary in these patients. Future research may allow the detection of diabetic kidney disease earlier in childhood, further expanding the role of the pediatric nephrologist. In particular, early renal biopsy may eventually be used to select those patients at risk of diabetic nephropathy for specific treatment alterations.     

Conversion from Cyclosporine to Tacrolimus Improves Quality-of-Life Indices, Renal Graft Function and Cardiovascular Risk Profile

Long-term use of cyclosporine after renal transplantation results in nephrotoxicity and an increased cardiovascular risk profile. Tacrolimus may be more favorable in this respect. In this randomized controlled study in 124 renal transplant patients, the effects of conversion from cyclosporine to tacrolimus on renal function, cardiovascular risk factors, and perceived side-effects were investigated after a follow-up of 2 years. After conversion from cyclosporine to tacrolimus renal function remained stable, whereas continuation of cyclosporine was accompanied by a rise in serum creatinine from 142 +/- 48 micromol/L to 157 +/- 62 micromol/L (p < 0.05 comparing both groups). Conversion to tacrolimus resulted in a sustained reduction in systolic and diastolic blood pressure, and a sustained improvement in the serum lipid profile, leading to a reduction in the Framingham risk score from 5.7 +/- 4.3 to 4.8 +/- 5.3 (p < 0.05). Finally, conversion to tacrolimus resulted in decreased scores for occurrence of and distress due to side-effects. In conclusion, conversion from cyclosporine to tacrolimus in stable renal transplant patients is beneficial with respect to renal function, cardiovascular risk profile, and side-effects. Therefore, for most renal transplant patients tacrolimus will be the drug of choice when long-term treatment with a calcineurin inhibitor is indicated.     

Cancer incidence in patients on chronic dialysis and in renal transplant recipients

A markedly increased incidence of cancer in renal transplant recipients is now recognized; to determine if immunosuppression alone may be responsible for this increase in risk, cancer incidence was compared in 709 renal transplant recipients and 317 dialysis patients. Malignancy developed in 19 transplant recipients (2.7%) and in 33 patients on chronic dialysis (10.4%). In our report an excess of skin cancer was observed in the transplant series while tumors of the urinary tract were seen more frequently in patients on dialysis. Transplantation and consecutive immunosuppression does not appear to constitute an additional cancer risk for the uremic patient who is faced with the alternative to undergo chronic dialysis or renal transplantation.     

Atherosclerosis and vascular calcification in chronic renal failure

Cardiovascular complications are a major clinical problem in patients with chronic kidney disease and end-stage renal failure; cardiac death accounts for approximately 40-50% of all deaths in these patients. Death from cardiovascular causes is up to 20 times more common in uremic patients than in the general population with the risk being even higher than in patients with diabetes mellitus. A high rate of myocardial infarction and excessive cardiac mortality have repeatedly been documented in patients with kidney disease and renal failure. Not only is the prevalence of myocardial infarction high, but also the case fatality rate is significantly higher in uremic patients with and without diabetes, respectively, compared to nonuremic patients. This is of particular interest since the prevalence of coronary atheroma in uremic patients was shown to be approximately 30% by autopsy and coronary angiography studies. Thus, coronary factors, i.e. atherosclerosis, and non-coronary factors may play an important role in the genesis of cardiac complications in the renal patient. In addition, renal failure recently has also be identified as a predictor of mortality in different stages of peripheral vascular disease. In particular, marked differences in the pathogenesis, morphology and course of atherosclerosis and arteriosclerosis under the conditions of renal failure have been documented. Among others increased plaque formation and particularly higher proportion and intensity of vascular calcification have been found in clinical and autopsy studies. In addition to the so-called classical or traditional risk factors, an important role for nonclassical risk factors such as microinflammation, hyperphosphatemia and oxidative stress has been documented in patients with renal failure and is discussed in detail.     

Renal disease in the elderly: the role of the renal biopsy

The causes of renal disease in the young and the elderly vary in their frequency. There are many indications for renal biopsy in older patients, with the nephrotic syndrome (NS) being the most common, followed by acute renal failure. Biopsy does not carry a greater risk for older patients, but there is a greater risk of complications when there is coexistent renal insufficiency. Interpretation of the renal biopsy in elderly patients may be more complex because of changes associated with aging or intercurrent disease--arteriolar sclerosis and global sclerosis. A prospective study is needed to determine the exact prevalence of renal insufficiency, NS, and other renal diseases in noninstitutionalized elderly individuals and to determine the role of renal biopsy in making these determinations.     

Renal disease in cardiovascular disorders: an underrecognized problem

Chronic renal disease is generally appreciated as a major and rapidly growing health problem. In the United States alone, as many as 19.5 million people may have markers of early renal disease, and more than 660,000 people are expected to require renal replacement therapy by the year 2010. By contrast, the presence and pathological role of renal disease in patients with cardiovascular disease are somewhat underrecognized. Evidence now shows that even minor impairments in renal function, as indicated by measures including glomerular filtration rate and microalbuminuria, are common in cardiovascular disease states and predictive of cardiovascular events. Indeed, microalbuminuria may be a marker of systemic vascular disease rather than kidney dysfunction alone. In patients with hypertension, diabetes, metabolic syndrome, acute coronary syndromes, and stroke, markers of renal disease have proved to be at least as predictive of morbidity and mortality as conventional risk factors. Yet, chart reviews in a variety of clinical settings reflect poor recognition and management of renal disease in at-risk patients. Models for renal protection are based on the control of risk factors, particularly blood pressure, that are associated with renal and cardiovascular outcomes. Screening protocols for markers of renal disease should recognize the potential inaccuracy of serum creatinine concentrations and the preferability of glomerular filtration rate estimates that take age and gender into account. Pilot programs for screening high-risk populations have shown efficacy in detecting renal disease.     

Vesicoureteral reflux and reflux nephropathy

Vesicoureteral reflux is an anatomic abnormality, mostly affecting a pediatric population, which may be the second leading cause of end-stage renal failure. Most cases of reflux are due to abnormalities in the insertion of the ureters into the bladder, either congenital or acquired. Most commonly, VUR is discovered during routine evaluation of urinary tract infections, but may also be present in patients with severe hypertension or chronic renal failure. The diagnosis is confirmed radiologically, utilizing either voiding cinecystography or radioisotopic methods. VUR can result in renal failure through scarring secondary to 'chronic pyelonephritis' or through a glomerulopathy, possibly immune in origin. In most series, the glomerulopathy is felt to be the cause of the end-stage renal failure. Treatment of VUR includes conservative (medical) management with the hope that maturation of the ureterovesical junction will cure reflux. Surgical therapy is reserved for those patients in whom this maturation is not expected to occur or in those whose urinary infections cannot be controlled. In those patients who have developed the glomerulopathy secondary to VUR, surgery may not halt the progression of the renal disease. VUR in a transplanted kidney may result in a higher risk of loss of the graft due to glomerulopathy or chronic rejection.     

Renal function trajectory is more important than chronic kidney disease stage for managing patients with chronic kidney disease

Management of patients with chronic kidney disease (CKD) emphasizes a current level of function as calculated from the modification of diet in renal disease glomerulofiltration rate equations (eGFR) and proteinuria for staging of CKD. Change in a patient's eGFR over time (renal function trajectory) is an additional and potentially more important consideration in deciding which patients will progress to the point where they will require renal replacement therapy (RRT). Many patients with CKD 3-5 have stable renal function for years. Proteinuria/albuminuria is a primary determinant of renal trajectory which may be slowed by medications that decrease proteinuria and/or aggressively lower blood pressure. A renal trajectory of >3 ml/min/1.73 m(2)/year may relate to a need for closer renal follow-up and increased morbidity and mortality. Additional CKD population-based studies need to examine the relationship of renal trajectory to: baseline renal function; acute kidney injury episodes; age, race, sex and primary etiologies of renal disease; blood pressure control and therapies; dietary protein intake; blood glucose control in diabetics and the competitive risk of death versus the requirement for renal replacement therapy. In the elderly CKD 4 population with significant comorbidities and slow decline in renal function, the likelihood of death prior to the need for RRT should be considered before placing AV access for dialysis. Prediction models of renal progression must account for the competitive risk of death as well as stable or improved renal function to be clinically useful.     

Cardiac problems in the dialysis patient: beyond coronary disease

In end-stage renal disease (ESRD) both an inappropriately high sympathetic drive and the activation of tissue-based renin-angiotensin systems lead to a complex pattern of comorbidity appearing early on in renal disease. In this context, uremic cardiomyopathy, diabetes, and renal failure display an intimate interaction that critically defines the prognosis in dialysis patients. Importantly, patients with moderate to severe loss of renal function not only carry a high burden of traditional cardiovascular risk factors, but also are exposed to uremia-specific risk factors that in concert induce an excessively increased cardiovascular mortality. Although cardiovascular guidelines may not simply be applicable to ESRD patients —these have invariably been excluded from larger cardiovascular trials—an early cardiological workup appears rational as the prevailing mode of death is characterized by sudden cardiac death and heart failure. This short review will therefore go beyond coronary heart disease, focus on the specific cardiac pathology in renal failure, and summarize the contemporary therapeutic strategies in ESRD.     

Anticoagulation in continuous renal replacement therapy

Continuous renal replacement therapies (CRRTs) allow for gradual solute and fluid removal. In very sick patients with acute renal failure, they may be better tolerated than hemodialysis. The major drawback to CRRTs is the need for anticoagulation to maintain filter patency. The patients who are likely to benefit from CRRTs are also at higher risk for bleeding from systemic anticoagulation. The most commonly used form of anticoagulation for CRRTs, low-dose heparin, causes bleeding in 10-50% of patients. Regional anticoagulation using protamine may reduce the risk of bleeding, but it is difficult to use. Low molecular weight heparin and prostacyclin both may partially reduce bleeding, but are difficult to dose. Regional anticoagulation with citrate is easy to use and has been shown to prolong filter life without systemic anticoagulation. It is the anticoagulant of choice for most patients on CRRT.     

Intrarenal small artery thrombosis in a transplant recipient patient infected with Covid-19 after kidney transplantation: A rare case report

Currently, renal arteriovenous thrombosis induced by Covid-19 infection in patients after renal transplantation is very rare. We present a recent kidney transplant recipient who developed Covid-19 infection and later developed intrarenal small artery thrombosis. Finally, the patient's respiratory tract infection symptoms gradually disappeared after treatment. However, hemodialysis replacement therapy has to be continued due to the injury of the transplanted kidney function. In this case, we first reported that Covid-19 infection may induce intrarenal small artery thrombosis after kidney transplantation, which caused local ischemic necrosis of the transplanted kidney. We found that patients are at a high risk of Covid-19 infection at the early stage after kidney transplantation, and their clinical symptoms may be severe. In addition, even with anticoagulant therapy, Covid-19 infection may still increase the risk of thrombosis to some extent for patients who have undergone kidney transplantation, and we need to be alert to this rare complication in the future clinical work.     

Recombinant hirudin (lepirudin) as anticoagulant in intensive care patients treated with continuous hemodialysis

BACKGROUND: Recombinant hirudin (lepirudin) is a potent direct thrombin inhibitor, which has been approved for the treatment of heparin-induced thrombocytopenia type II (HIT). Because the drug is mainly eliminated by the kidneys, a single loading dose of hirudin may induce therapeutic anticoagulation for up to one week in patients with renal insufficiency. Thus, the use of hirudin in critically ill patients with renal failure could markedly increase their bleeding risk. In this study, hirudin was used in critically ill patients with suspected HIT while on continuous venovenous hemodialysis (CVVHD). METHODS: Hirudin anticoagulation was performed in seven critically ill patients with suspected HIT. Four patients were initially anuric. Three patients had residual renal function. In all 64 CVVHD treatments (mean duration 12 hr), a polysulfone high-flux hemodialyzer (0.75 m2) with a dialysate flow rate of 1.5 liter/hr and an ultrafiltration rate of up to 200 ml/hr was used. Hirudin was given either as continuous intravenous infusion or as repetitive intravenous boli. Monitoring of anticoagulation was performed by measurements of the systemic activated partial thromboplastin time (aPTT). RESULTS: Hirudin dosage had to be individualized according to the risk of bleeding or clotting. During CVVHD, a continuous intravenous infusion (0.006 to 0.025 mg/kg body wt/hr, N = 2) or repetitive intravenous boli (0.007 to 0.04 mg/kg, N = 5) were given. Two patients required blood transfusions prior to and during hirudin treatment. In five patients without a high bleeding risk, the hirudin dose was adjusted to achieve the target aPTT (1.5 to 2.0 x baseline) in order to prevent thrombotic complications or frequent clotting in the extracorporal circuit. Hirudin dose requirements depended on residual renal function and extracorporal clearance. CONCLUSIONS: We conclude from these first clinical data that anticoagulation with hirudin in critically ill patients on continuous hemodialysis can be performed without excessive bleeding risk by combining close clinical and laboratory monitoring. The hirudin dose has to be reduced because of renal failure, and may require adjustment for residual or recovering renal function and extracorporal elimination.     

Estrogen replacement therapy: implications for postmenopausal women with end-stage renal disease

Little information is available about either the potential beneficial or harmful effects of estrogen replacement therapy in postmenopausal women with end-stage renal disease. Although evidence supports a role for estrogen replacement therapy in postmenopausal women in the prevention of cardiovascular disease and bone loss, possible improvement in cognitive function, and the relief of menopausal symptoms, these conclusions may not be applicable to patients with end-stage renal disease, since these studies have generally excluded such women. This issue is of considerable importance since cardiovascular causes account for more than 50% of the all-cause mortality in patients with end-stage renal disease. However, estrogen replacement therapy may also have untoward effects in patients with the disease, including an increased risk of dialysis access thrombosis and potentially worsening coronary artery disease in postmenopausal patients. Furthermore, dosing of estrogens needs to be done carefully since renal excretion is important for the elimination of estrogen metabolites. Low dose or alternate day dosing in addition to monitoring estrogen levels may be warranted when prescribing estrogen replacement therapy to women with end-stage renal disease. In this review, it is our objective to analyze the evidence published in the literature so far and to weigh the risks and benefits of estrogen therapy in postmenopausal women with end-stage renal disease.     

Treatment of type II diabetic patients with chronic renal failure

Glycaemic control is a key element in the management of patients with chronic renal insufficiency, associated of course with treatment of all the other associated factors. Dietary management should not merely be wishful thinking but a reality, involving the control of body weight, the maintenance of lean body mass, the observance of a sufficient carbohydrate intake and the control of protein intake, which, always tends to be excessive in diabetics. Drug treatment with oral antidiabetics may be given without risk of iatrogenic effects: glitazone has no effect on renal metabolism but may increase water retention; glinides are insulin secretagogues without renal metabolism so there is no risk of hypoglycaemia in the event of impaired renal function; if not insulin remains an excellent alternative with, however, a change in its half-life with the elevated creatinine clearance. In all cases, the goal remains the control of glycosylated haemoglobin without iatrogenic effects.     

Calcineurin Inhibitor Sparing With Mycophenolate Mofetil in Liver Transplantion: A Systematic Review of Randomized Controlled Trials

Liver transplant recipients are at high risk of developing acute and chronic renal failure. Moreover, introduction of the model for end‐stage liver disease (MELD) score for primary allocation of liver grafts favors patients with pretransplant kidney dysfunction, which in turn have a higher risk of posttransplant renal failure. Calcineurin inhibitors (CNI) further increase the risk of renal failure and therefore sparing CNI with the use of mycophenolate mofetil (MMF) may improve renal function. MMF may either be used de novo in the immediate posttransplant period in combination with low‐dose CNI (scenario 1) or patients that receive immunosuppression based on CNI may be converted to MMF in combination with minimization or elimination of CNI (scenario 2). Although many retrospective cohort studies and nonrandomized trials have implicated efficacy of this approach the evidence from randomized controlled studies has not been summarized. In the current review we report the results of a systematic review and meta‐analysis of randomized controlled trials.     

Renovascular disease and renal insufficiency--diagnosis and treatment

Renovascular disease as cause of end-stage renal disease has become more frequent during the last decade. In order to minimize the need for dialysis treatment non-invasive screening for the disease is needed. However, both ultrasonic duplex scanning and renal scintigraphy are not sufficient for detection of all stenosis. Furthermore, there is little data on non-invasive tests in patients with renal insufficiency. Renal arteriography is the gold standard for detection of renovascular disease. One disadvantage is the risk of contrast-agent induced acute renal insufficiency. This problem can be avoided using carbon dioxide angiography. In the near future spiral computed tomography and magnetic resonance angiography may be alternatives for identifying patients with renovascular disease. Ischaemic nephropathy is potentially curable. Percutaneous transluminal renal angioplasty is first line treatment in most cases. Intervention often results in improvement or preservation of renal function which is very important in order to avoid chronic dialysis.