ADQI 7: the clinical management of the Cardio-Renal syndromes: work group statements from the 7th ADQI consensus conference.

Many patients with heart failure have underlying renal dysfunction, and similarly, patients with kidney failure are prone to cardiac failure. This has led to the concept of cardio-renal syndromes, which can be an acute or chronic cardio-renal syndrome, when cardiac failure causes deterioration in renal function, or acute and/or chronic Reno-Cardiac syndrome, when renal dysfunction leads to cardiac failure. Patients who develop these syndromes have increased risk of hospital admission and mortality. Although there are clinical guidelines for managing both heart failure and chronic kidney disease, there are no agreed guidelines for managing patients with cardio-renal and/or Reno-Cardiac syndromes, as these patients have typically been excluded from clinical trials. We have therefore reviewed the currently available published literature to outline a consensus of current best clinical practice for these patients.

Comparison of estimated glomerular filtration rate (eGFR) using the MDRD and CKD-EPI equations for CKD screening in a large population.

BACKGROUND/AIMS: recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) proposed a new equation for estimating glomerular filtration rate (eGFR), which could potentially replace the Modified Diet for Renal Disease Study (MDRD) equation in routine clinical use. Our aim was to evaluate the correlation between them and to compare the prevalence of each CKD stage using these two equations. METHODS: we measured serum creatinine in 38,188 consecutive patients and calculated eGFR using the CKD-EPI and MDRD equations. We also compared the distribution of CKD stages for both equations. RESULTS: there was very good correlation between eGFR estimated by CKD-EPI and MDRD at values < 60 ml/min × 1.73 m2, but not at higher values. Estimated prevalence of CKD (eGFR < 60 ml/min × 1.73 m2) was 5.9% with CKD-EPI and 7.5% with MDRD. Furthermore, the prevalence of CKD Stage 2 was lower with CKD-EPI (33.8% vs. 49.1%. with MDRD). CONCLUSION: the use of the CKD-EPI equation results in a lower estimated prevalence of CKD, compared to the MDRD equation. This may have important implications for public health and clinical practice, as well as for future modification of guidelines for laboratories.

Clinical pattern of adult polycystic kidney disease in a northeastern region of Italy.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disorder, with a prevalence of 1 : 500 to 1 : 1,000. ADPKD is genetically heterogeneous: the genes involved are PKD1 and PKD2. ADPKD occurs worldwide and in all ethnic groups and is an important cause of CKD Stage 5. Prevalence of ADPKD on renal replacement therapy (RRT) in Italy has been reported to be 8.2%. In the dialysis population of Vicenza, a province in Northeastern Italy, it accounts for 13.4%. The study aims to investigate reasons for the high prevalence of ADPKD in our region and to describe the clinical profile and genetics of these patients. METHODS: Since April 2007, ADPKD patients have been enrolled. Patients from families not native to Vicenza have been excluded. The diagnosis of ADPKD is defined by ultrasound criteria. Complete clinical details have been recorded, including family history. We have used linkage analysis to identify the gene involved in each family. RESULTS: We describe the first 100 patients recruited from a total of 42 families. 29 patients were in ESRD at the time of enrollment. Renal stones and hepatic cysts were present in 24% and 40%, respectively. The majority of the ADPKD patients (61%) were diagnosed either incidentally or by screening. Positive family history was recorded in 86 patients. The involved gene was PKD1 in 83.7% and PKD2 in 16.3% of the studied patients. PKD2 patients presented the common haplotype. CONCLUSIONS: It is the first epidemiological study from Northeastern Italy reporting clinical profile and genetic analysis of ADPKD patients. The clinical profile of the patients is similar to previous reports, but there is a high prevalence of ADPKD in our region. The presence of a common haplotype is in accordance with our hypothesis of a founder effect in our province, suggesting that a strong lineage-specific gene is present. If the sequence analysis confirms the same mutation, this might suggest a common ancestral origin and a segregation of a specific mutation.

The role of extracorporeal blood purification therapies in the prevention of radiocontrast-induced nephropathy.

Radiocontrast-induced nephropathy (RCIN) is a common and potentially serious complication following diagnostic and therapeutic cardiology procedures using radiocontrast media. The first and most important step in reducing the likelihood of RCIN is to identify patients at risk, by medical history and measurement of serum creatinine concentration to allow calculation of estimated glomerular filtration rate (GFR). Extracorporeal blood purification effectively removes radiocontrast media from the circulation. Periprocedural extracorporeal blood purification (hemodialysis or continuous renal replacement therapy) does not reduce the incidence of RCIN compared with standard medical therapy, and cannot be recommended at this time. The potential benefit of continuous venovenous hemofiltration published by a single center should be confirmed with further studies before it can be recommended or disregarded, and higher doses of continuous renal replacement therapy may also merit further investigation.

The epidemiology of cardiac surgery-associated acute kidney injury.

PURPOSE: To describe current knowledge on the epidemiology of cardiac surgery-associated acute kidney injury (CSA-AKI) and to formulate recommendations for clinical practice and a research agenda. METHODS: After a modified Delphi analysis by the Acute Dialysis Quality Initiative (ADQI), 4 questions on the epidemiology of CSA-AKI and recommendations for clinical practice and a research agenda were formulated and addressed. RESULTS: Existing studies on CSA-AKI use over 35 different definitions for CSA-AKI. In addition, there may be important differences in patient characteristics and procedures. This explains the significant variations in reported incidence. Most studies report on CSA-AKI as defined by the need for renal replacement therapy. However, even small decreases in kidney function are associated with a worsened outcome. The workgroup formulated the recommendation to use the AKIN consensus criteria for AKI. One should differentiate early CSA-AKI, caused by the procedure, and late CSA-AKI, associated with the procedure. There may be different clinical scenarios: acute on chronic CSA-AKI, AKI prior to CS, and AKI occurring post CS. Risk factors should be differentiated between pre-, intra-, and post-CS, and between patient-, process-, and procedure-related. Endpoints should include both short-term and long-term outcomes. CONCLUSIONS: Existing data on the epidemiology of CSA-AKI are difficult to compare due to variations in definition and patient cohort. A modified Delphi analysis resulted in a series of recommendations for future research on CSA-AKI.

Effect of vitamin E-coated dialysis membranes on anemia in patients with chronic kidney disease: an Italian multicenter study.

BACKGROUND: Increased oxidant stress is increasingly recognized as a crucial factor in anemia in patients with chronic kidney disease. Vitamin E-coated membranes (VECMs) consist of a multilayer membrane with liposoluble vitamin E on the blood surface allowing direct free radical scavenging at the membrane site, which is of potential clinical benefit. Our objective was to examine the effect of VECMs on anemia in chronic hemodialysis (HD). METHODS: We enrolled 172 stable chronic HD patients (94 men, 78 women, age 65.4 +/- 13.4 years) in an open-label multicenter study. They were shifted from their previous dialyzer to VECM for 1 year. Hemoglobin (Hb) levels and recombinant human erythropoietin (rHuEpo) dosage were analyzed after 4, 8, and 12 months on the VECM and compared with baseline values using paired tests. RESULTS: Hb significantly increased from 10.9 +/- 1.2 g/dL at baseline to 11.7 +/- 1.2 g/dL after 12 months (p<0.001) on VECMs. Conversely, the rHuEpo dosage decreased from 7,762 +/- 5,865 IU/week at baseline to 6,390 +/- 5,679 IU/week after 12 months (p<0.001). The proportion of patients who were at target Hb levels (European Best Practice Guidelines) increased from 49.4% at baseline to 80% after 12 months (p<0.001). CONCLUSIONS: Dialysis with VECM in stable chronic HD patients was associated with significantly improved Hb levels and lower rHuEpo requirements. These results suggest that the antioxidant properties of VECMs may impact favorably on anemia management in chronic HD patients. Possible mechanisms include enhanced membrane biocompatibility, reduced oxidative stress and inflammation with VECMs, resulting in improved red blood cell survival and/or rHuEpo responsiveness. This therapy may potentially contribute to more effective anemia management in hemodialysis patients, and merits further rigorous study.

Metabolic complications of urinary diversions: an overview.

Patients with urinary diversions present unique challenges to internists who have an important role in their long-term management. Advances in surgical techniques over the past 30 years have given rise to a number of urinary diversion procedures that use various intestinal segments. In its normal function, the intestine absorbs water and solutes. When placed in contact with the urinary stream, the intestine can create numerous metabolic abnormalities. These include bone disease, hepatobiliary disease, infection, malignancy, neurologic complications, nutritional deficiencies, and a number of electrolyte and acid-base disorders. An overview of these metabolic abnormalities and their causes is provided, as well as recommendations for screening and management of patients.

Parameters of high bone-turnover predict bone loss in renal transplant patients: a longitudinal study.

BACKGROUND: Osteoporosis is a serious complication of kidney transplantation. Various factors have been postulated to contribute to posttransplant bone loss, among them treatment with corticosteroids, the use of cyclosporine and cyclosporine-like agents, and persistent hyperparathyroidism. In a previous cross-sectional study of long-term renal transplant recipients, we observed that osteoporosis or osteopenia was present in 88% of patients. Because biochemical markers of bone formation (serum osteocalcin) and bone resorption (urine pyridinoline, PYD, and deoxypyridinoline, DPD) were elevated in the majority of study subjects, we hypothesized that elevated rates of bone-turnover contribute to posttransplant bone loss in long-term renal transplant patients. This study was performed to examine this hypothesis. METHODS: The study population was composed of 62 patients who were more than 1-year postrenal transplantation and who had preserved renal function. They were followed prospectively for 1 year. Biochemical markers of bone-turnover were measured at study entry, and patients were classified as having high bone-turnover based on elevated urinary levels of at least one marker of bone resorption (i.e., PYD or DPD) and/or serum osteocalcin (group 1). If none of these were present, they were classified as having normal bone-turnover (group 2). Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DEXA) at time of entry into the study and again after 1 year of follow-up. The changes in BMD at the lumbar spine, hip, and wrist over the period of the study were compared between the high and normal bone-turnover groups. RESULTS: Forty-three patients (69%) were classified as having high bone-turnover (Group 1), and 19 patients (31%) were classified as having normal bone-turnover (Group 2). There was a statistically significant difference in change in BMD between the two groups at the lumbar spine (-1.11+/-0.42%, high bone-turnover, vs. 0.64+/-0.54%, normal bone-turnover; P=0.02) and the hip (-0.69+/-0.38%, high bone-turnover, vs. 1.36+/-0.66%, normal bone-turnover; P=0.006). Whereas group 2 had stable bone mass, group 1 exhibited bone loss at these skeletal sites. CONCLUSIONS: Our results indicate that bone loss is greater in renal transplant recipients with elevated biochemical markers of bone-turnover, suggesting that these markers may be useful in identifying patients at risk for continued bone loss. These data support the hypothesis that continued bone loss in long-term renal transplant recipients is associated with high bone-turnover. If accelerated bone resorption does play a role in posttransplant bone loss, this would provide a strong rationale for use of antiresorptive therapy for the prevention and treatment of this complication.

Midodrine and cool dialysate are effective therapies for symptomatic intradialytic hypotension.

Intradialytic hypotension (IDH) is a morbid complication of hemodialysis (HD). Both midodrine, an oral selective alpha1 agonist, and cool dialysate have been reported as useful therapies for this problem. We performed this prospective crossover study to compare the efficacy of these two therapies, alone and in combination, for IDH. The study consisted of a control phase and three treatment phases: midodrine phase (10 mg oral dose pre-HD), cool dialysate phase (35.5 degrees C), and combination therapy phase (midodrine, 10 mg, and dialysate temperature, 35.5 degrees C). Each phase consisted of nine consecutive HD treatments. Eleven patients (six men, five women; mean age, 67.5 years) with known symptomatic IDH were studied. This cohort was followed up in terms of blood pressure measurements (pre-HD blood pressure, lowest intradialytic blood pressure, post-HD blood pressure), weights, laboratory values, and interventions for IDH. The lowest intradialytic blood pressures were significantly better with midodrine and cool dialysate compared with the control phase (systolic blood pressure [SBP], 103.9 +/- 4.1 [mean +/- standard error of the mean] and 102.6 +/- 2.9 v 90.6 +/- 2.5 mm Hg, respectively; P < 0.001), as were the post-HD blood pressures (SBP, 116.9 +/- 4.0 and 118.2 +/- 3.5 v 109.0 +/- 2.1 mm Hg; P < 0.01). In addition, the lowest intradialytic blood pressures were significantly better with the combination phase compared with the control phase (SBP, 103.7 +/- 4.2 v 90.6 +/- 2.5 mm Hg; P < 0.001), as were the post-HD blood pressures (SBP, 122.1 +/- 4.6 v 109.0 +/- 2.1 mm Hg; P < 0.01). There was a significant reduction in the number of nursing interventions performed and volume of saline infused for IDH with midodrine and cool dialysate compared with control. There was a trend toward amelioration of hypotensive symptoms with both therapies. Laboratory values, including Kt/V, did not change significantly with either midodrine or cool dialysate. This prospective study shows that both midodrine and cool dialysate are effective therapies for symptomatic IDH. There does not seem to be additional benefit when these two therapies are used in combination.

Midodrine: a selective alpha-adrenergic agonist for orthostatic hypotension and dialysis hypotension.

Midodrine is an oral agent which acts as a selective peripherally-acting alpha-receptor agonist. Midodrine is a prodrug that is almost completely absorbed after oral administration and converted into its active drug de-glymidodrine in the systematic circulation, with a bioavailability of 93%. It has been used successfully in the treatment of neurogenic orthostatic hypotension and more recently, in the treatment of dialysis hypotension. It acts through vasoconstriction of the arterioles and the venous capacitance vessels, thereby increasing peripheral vascular resistance and augmenting venous return, respectively. It is a unique agent in the armamentarium against orthostatic hypotension since it has minimal cardiac and CNS effects. This article will review the literature on midodrine for conditions of autonomic dysfunction, with focus on recent studies on its use in haemodialysis patients.

Midodrine is effective and safe therapy for intradialytic hypotension over 8 months of follow-up.

Intradialytic hypotension (IDH) is a common and frustrating complication of hemodialysis. Certain end stage renal disease (ESRD) patients recurrently manifest this disabling condition. Both patient-specific factors (autonomic insufficiency, cardiac disease) and dialysis treatment-related factors (ultrafiltration, increased core body temperature) are thought to have significant causative roles. Most therapeutic interventions to date have been either unsuccessful or poorly tolerated. However, recent studies have shown that midodrine, an oral peripheral alpha-1 adrenergic agonist, is an effective and safe therapy for symptomatic IDH in the short-term. We report our experience with the predialysis use of midodrine for IDH in 13 hemodialysis (HD) patients over a 5 to 8 month period. Thirteen patients (8 male, 5 female, mean age 63.9 yrs) with recurrent symptomatic IDH were given midodrine 10 mg orally 30 min before each HD session. Blood pressures (pre-HD BP, lowest intradialytic [ID] BP, post-HD BP) and body weights were tracked for each HD treatment. Values for 10 HD sessions prior to midodrine therapy (Baseline) were compared to values (10 HD sessions each) during the 1st, 5th and 8th month of midodrine therapy. Data were analyzed using ANOVA for repeated measures and paired t-tests, with each patient serving as his/her own control. Patients were monitored for 5 months (n = 13) and 8 months (n = 8), respectively. All lowest intradialytic BPs, post-HD SBPs, and MAPs were significantly improved (p <0.05) on midodrine therapy. This effect was maintained during all periods of follow-up. There was no significant difference in mean albumin, hematocrit, Kt/V, calcium, and sodium between baseline and all periods of follow-up. Mean ultrafiltration volume per HD session was not significantly different than baseline over the course of study. A subjective improvement in hypotensive symptoms was also noted. Importantly, there were no adverse reactions to midodrine in all periods of follow-up. Midodrine appears to be an effective and safe treatment for HD patients with symptomatic IDH, and remains beneficial when used for an extended period of time.

Hypertension and hypokalemia: unusual syndromes.

Secondary hypertension accounts for a minority of all cases of hypertension. Certain clues in the patient's medical history and laboratory parameters may help identify the rare patient with secondary hypertension. The association of hypertension with hypokalemia and renal potassium wasting should raise one's suspicion for a state of mineralocorticoid excess. The clinical syndrome of hypertension and hypokalemia may be related either to a high renin state, such as renovascular disease, or to a low renin state, such as primary hyperaldosteronism, adrenal enzyme defects, certain familial syndromes, and licorice ingestion. Over the past decade, a genetic basis has been identified for apparent mineralocorticoid excess (AME) syndrome, Liddle's syndrome, and glucocorticoid remediable aldosteronism (GRA). This brief review focuses on a few of the unusual conditions which cause a true or apparent mineralocorticoid excess state, and summarizes the clinical presentation, pathogenetic mechanism, and treatment of these diseases.

Body composition and heart rate variability to achieve dry weight and tolerance.

Autonomic dysfunction in patients with end- stage renal disease is associated with poor prognosis. Heart rate variability (HRV), determined by the standard deviation of the normal R- R interval, has been reported to be a useful evaluation of cardiac autonomic modulation. The relationship between HRV and hydration status (HS) can be analyzed by whole body bioimpedance spectroscopy. This allows a classification of patients according the combination of HS with predialysis systolic blood pressure. Differences in HRV can be studied in patients with high over hydration, but normal or low blood pressure, with respect to fluid-overloaded/hypertensive patients and normohydrated/normotensive patients. In conclusion, the assessment of the autonomic nervous system response to the hemodialysis treatment in end- stage renal disease patients, classified according to a reliable and quantitative measurement of their fluid overload, could permit better management of both arterial blood pressure and HS.

Prospective multicenter study on epidemiology of acute kidney injury in the ICU: a critical care nephrology Italian collaborative effort (NEFROINT).

Acute kidney injury (AKI) is an independent risk factor for mortality in critically ill patients whose epidemiology has been made unclear in the past by the use of different definitions across various studies. The RIFLE consensus definition has provided a unifying definition for AKI leading to large retrospective studies in different countries. The present study is a prospective observational multicenter study designed to prospectively evaluate all incident admissions in 10 Intensive Care Units (ICUs) in Italy and the relevant epidemiology of AKI. A simple user-friendly web-based data collection tool was created with the scope to serve for this study and to facilitate future multicenter collaborative efforts. We enrolled 601 consecutive patients into the study; 25 patients with End-Stage Renal Disease were excluded leaving 576 patients for analysis. The median age was 66 (IQR 53-76) years, 59.4% were male, while median SAPS II and APACHE II scores were 43 (IQR 35-54) and 18 (IQR 13-24), respectively. The most common diagnostic categories for ICU admission were: respiratory (27.4%), followed by neurologic (17%), trauma (14.4%), and cardiovascular (12.1%). Crude ICU and hospital mortality were 21.7% and median ICU length of stay was 5 days (IQR 3, 14). Of 576 patients, 246 patients (42.7%) had AKI within 24 hours of ICU admission while 133 developed new AKI later during their ICU stay. RIFLE-initial class was Risk in 205 patients (54.1%), Injury in 99 (26.1%) and Failure in 75 (19.8%). Progression of AKI to a worse RIFLE class was seen in 114 patients (30.8% of AKI patients). AKI patients were older, with higher frequency of common risk factors. 116 AKI patients (30.6%) fulfilled criteria for sepsis during their ICU stay, compared to 33 (16.7%) of non-AKI patients (P<0.001). 48 patients (8.3%) were treated with renal replacement therapy (RRT) in the ICU. Patients were started on RRT a median of 2 (IQR 0-6) days after ICU admission. Among AKI patients, they were started on RRT a median of 1 (IQR 0-4) days after fulfilling criteria for AKI. Median duration of RRT was 5 (IQR 2-10) day. AKI patients had a higher crude ICU mortality (28.8% vs. non-AKI 8.1%, P<0.001) and longer ICU length of stay (median 7 days vs. 3 days [non-AKI], P<0.001). Crude ICU mortality and ICU length of stay increased with greater severity of AKI. Two hundred twenty five patients (59.4% of AKI patients) had complete recovery of renal function, with a SCr at time of ICU discharge which was ≤120% of baseline; an additional 51 AKI patients (13.5%) had partial renal recovery, while 103 (27.2%) had not recovered renal function at the time of death or ICU discharge. Septic patients had more severe AKI, and were more likely to receive RRT with less frequency of renal function recovery. Patients with sepsis had higher ICU mortality and longer ICU stay. The study confirms previous analyses describing RIFLE as an optimal classification system to stage AKI severity. AKI is indeed a deadly complication for ICU patients where the level of severity correlated with mortality and length of stay. The tool developed for data collection resulted user friendly and easy to implement. Some of its features including a RIFLE class alert system, may help the treating physician to collect systematically AKI data in the ICU and possibly may guide specific decision on the institution of renal replacement therapy.

Biochemical aberrations in a dialysis patient following parathyroidectomy.

Renal osteodystrophy is a common problem in patients with end-stage renal disease. Severe secondary hyperparathyroidism unresponsive to an intensive regimen of diet, phosphate binders, and calcitriol therapy is an indication for surgical parathyroidectomy. Certain unique postoperative electrolyte aberrations are seen after parathyroidectomy, including severe hypocalcemia and hypophosphatemia (hungry bone syndrome), as well as hyperkalemia. Identifying the patient at high risk for developing these electrolyte abnormalities will facilitate perioperative and postoperative management.

Drug-induced acute tubulointerstitial nephritis: the clinical spectrum.

Clinical and laboratory findings vary with the drug involved. A definitive diagnosis requires renal biopsy; a gallium scan may be helpful when biopsy is not feasible. Outcome depends on drug withdrawal, but corticosteroids may be beneficial.

A patient with Wegener's granulomatosis presenting with a subarachnoid hemorrhage: case report and review of CNS disease associated with Wegener's granulomatosis.

Up to 54% of the patients with Wegener's granulomatosis (WG) experience neurological manifestations at some point during the course of their disease. However, the central nervous system is involved in less than 10% of the patients. There have only been 4 reported cases of subarachnoid hemorrhage complicating WG. We now report the 1st patient with a clinical picture and histopathologic features consistent with WG presenting with a subarachnoid hemorrhage. Another unusual feature of this case is that perinuclear staining rather than cytoplasmic staining antineutrophil cytoplasmic autoantibodies were positive. The literature on central nervous involvement in WG is reviewed.

Acute renal failure after cardiac transplantation: a case report and review of the literature.

Acute renal failure (ARF) is a relatively frequent complication associated with heart transplantation. It develops in the first few days postoperatively and is characterized by oliguria with laboratory and urinary indices typical of pre-renal azotemia. Cyclosporine, especially with higher doses, is one of the many factors which play an integral part in the nephrotoxicity following cardiac transplant. Poor preoperative renal function and perioperative hemodynamic compromise may also contribute to ARF. The actual incidence of ARF now encountered by transplant centers may be lower than previously reported, the result of lower cyclosporine doses. Currently, management is entirely supportive, but novel therapeutic approaches with atrial natriuretic peptide-like substances are being explored. A case illustrating the typical clinical presentation of ARF after heart transplant will be presented and the clinical features will be reviewed.

A middle-aged woman with back and flank pain.

Xanthogranulomatous pyelonephritis is an uncommon variant of chronic pyelonephritis that predominantly affects middle-aged women. Patients usually present with fever, back or flank pain, flank mass, and the constitutional symptoms of fatigue, malaise, weight loss, and anorexia. Rarely, they may present with a draining sinus. There is usually a history of urinary tract infection, obstruction, or instrumentation. Other abnormalities include anemia, leukocytosis, abnormal liver enzymes, pyuria, and hematuria. Mild azotemia may be present, but frank renal failure is rare. Urine and renal tissue cultures are frequently positive. The most commonly isolated bacterial pathogens are P. mirabilis and E. coli, but other organisms have also been implicated. A CT scan is the best radiologic imaging technique to discover the extent of inflammation as well as any involvement of adjacent structures. Lipid-laden macrophages called xanthoma cells characterize the disease at the microscopic level. Nephrectomy is curative. Careful preoperative evaluation will guide surgical planning in choosing an approach that provides adequate exposure of the affected tissue and facilitates subsequent care of the patient.