Recognition and management of community-acquired acute kidney injury in low-resource settings in the ISN 0by25 trial: A multi-country feasibility study.

BACKGROUND: Acute kidney injury (AKI) is increasingly encountered in community settings and contributes to morbidity, mortality, and increased resource utilization worldwide. In low-resource settings, lack of awareness of and limited access to diagnostic and therapeutic interventions likely influence patient management. We evaluated the feasibility of the use of point-of-care (POC) serum creatinine and urine dipstick testing with an education and training program to optimize the identification and management of AKI in the community in 3 low-resource countries. METHODS AND FINDINGS: Patients presenting to healthcare centers (HCCs) from 1 October 2016 to 29 September 2017 in the cities Cochabamba, Bolivia; Dharan, Nepal; and Blantyre, Malawi, were assessed utilizing a symptom-based risk score to identify patients at moderate to high AKI risk. POC testing for serum creatinine and urine dipstick at enrollment were utilized to classify these patients as having chronic kidney disease (CKD), acute kidney disease (AKD), or no kidney disease (NKD). Patients were followed for a maximum of 6 months with repeat POC testing. AKI development was assessed at 7 days, kidney recovery at 1 month, and progression to CKD and mortality at 3 and 6 months. Following an observation phase to establish baseline data, care providers and physicians in the HCCs were trained with a standardized protocol utilizing POC tests to evaluate and manage patients, guided by physicians in referral hospitals connected via mobile digital technology. We evaluated 3,577 patients, and 2,101 were enrolled: 978 in the observation phase and 1,123 in the intervention phase. Due to the high number of patients attending the centers daily, it was not feasible to screen all patients to assess the actual incidence of AKI. Of enrolled patients, 1,825/2,101 (87%) were adults, 1,117/2,101 (53%) were females, 399/2,101 (19%) were from Bolivia, 813/2,101 (39%) were from Malawi, and 889/2,101 (42%) were from Nepal. The age of enrolled patients ranged from 1 month to 96 years, with a mean of 43 years (SD 21) and a median of 43 years (IQR 27-62). Hypertension was the most common comorbidity (418/2,101; 20%). At enrollment, 197/2,101 (9.4%) had CKD, and 1,199/2,101 (57%) had AKD. AKI developed in 30% within 7 days. By 1 month, 268/978 (27%) patients in the observation phase and 203/1,123 (18%) in the intervention phase were lost to follow-up. In the intervention phase, more patients received fluids (observation 714/978 [73%] versus intervention 874/1,123 [78%]; 95% CI 0.63, 0.94; p = 0.012), hospitalization was reduced (observation 578/978 [59%] versus intervention 548/1,123 [49%]; 95% CI 0.55, 0.79; p < 0.001), and admitted patients with severe AKI did not show a significantly lower mortality during follow-up (observation 27/135 [20%] versus intervention 21/178 [11.8%]; 95% CI 0.98, 3.52; p = 0.057). Of 504 patients with kidney function assessed during the 6-month follow-up, de novo CKD arose in 79/484 (16.3%), with no difference between the observation and intervention phase (95% CI 0.91, 2.47; p = 0.101). Overall mortality was 273/2,101 (13%) and was highest in those who had CKD (24/106; 23%), followed by those with AKD (128/760; 17%), AKI (85/628; 14%), and NKD (36/607; 6%). The main limitation of our study was the inability to determine the actual incidence of kidney dysfunction in the health centers as it was not feasible to screen all the patients due to the high numbers seen daily. CONCLUSIONS: This multicenter, non-randomized feasibility study in low-resource settings demonstrates that it is feasible to implement a comprehensive program utilizing POC testing and protocol-based management to improve the recognition and management of AKI and AKD in high-risk patients in primary care.

Harmonizing acute and chronic kidney disease definition and classification: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference.

Kidney disease is an important public health problem. Both acute kidney injury (AKI) and chronic kidney disease have been well defined and classified, leading to improved research efforts and subsequent management strategies and recommendations. For those patients with abnormalities in kidney function and/or structure who meet neither the definition of AKI nor chronic kidney disease, there remains a gap in research, care, and guidance. The term acute kidney diseases and disorders, abbreviated to acute kidney disease (AKD), has been introduced as an important construct to address this. To expand and harmonize existing definitions and to ultimately better inform research and clinical care, Kidney Disease: Improving Global Outcomes (KDIGO) organized a consensus workshop. Multiple invitees from around the globe, representing both acute and chronic kidney disease researchers and experts, met virtually to examine existing data, and discuss key concepts related to AKD. Despite some remaining unresolved questions, conference attendees reached general consensus on the definition and classification of AKD, management strategies, and research priorities. AKD is defined by abnormalities of kidney function and/or structure with implications for health and with a duration of ≤3 months. AKD may include AKI, but, more importantly, also includes abnormalities in kidney function that are not as severe as AKI or that develop over a period of >7 days. The cause(s) of AKD should be sought, and classification includes functional and structural parameters. Management of AKD is currently based on empirical considerations. A robust research agenda to enable refinement and validation of definitions and classification systems, and thus testing of interventions and strategies, is proposed.

Recognition and management of acute kidney injury in the International Society of Nephrology 0by25 Global Snapshot: a multinational cross-sectional study.

BACKGROUND: Epidemiological data for acute kidney injury are scarce, especially in low-income countries (LICs) and lower-middle-income countries (LMICs). We aimed to assess regional differences in acute kidney injury recognition, management, and outcomes. METHODS: In this multinational cross-sectional study, 322 physicians from 289 centres in 72 countries collected prospective data for paediatric and adult patients with confirmed acute kidney injury in hospital and non-hospital settings who met criteria for acute kidney injury. Signs and symptoms at presentation, comorbidities, risk factors for acute kidney injury, and process-of-care data were obtained at the start of acute kidney injury, and need for dialysis, renal recovery, and mortality recorded at 7 days, and at hospital discharge or death, whichever came earlier. We classified countries into high-income countries (HICs), upper-middle-income countries (UMICs), and combined LICs and LMICs (LLMICs) according to their 2014 gross national income per person. FINDINGS: Between Sept 29 and Dec 7, 2014, data were collected from 4018 patients. 2337 (58%) patients developed community-acquired acute kidney injury, with 889 (80%) of 1118 patients in LLMICs, 815 (51%) of 1594 in UMICs, and 663 (51%) of 1241 in HICs (for HICs vs UMICs p=0.33; p<0.0001 for all other comparisons). Hypotension (1615 [40%] patients) and dehydration (1536 [38%] patients) were the most common causes of acute kidney injury. Dehydration was the most frequent cause of acute kidney injury in LLMICs (526 [46%] of 1153 vs 518 [32%] of 1605 in UMICs vs 492 [39%] of 1260 in HICs) and hypotension in HICs (564 [45%] of 1260 vs 611 [38%%] of 1605 in UMICs vs 440 [38%] of 1153 LLMICs). Mortality at 7 days was 423 (11%) of 3855, and was higher in LLMICs (129 [12%] of 1076) than in HICs (125 [10%] of 1230) and UMICs (169 [11%] of 1549). INTERPRETATION: We identified common aetiological factors across all countries, which might be amenable to a standardised approach for early recognition and treatment of acute kidney injury. Study limitations include a small number of patients from outpatient settings and LICs, potentially under-representing the true burden of acute kidney injury in these areas. Additional strategies are needed to raise awareness of acute kidney injury in community health-care settings, especially in LICs. FUNDING: International Society of Nephrology.

Acute kidney injury: an increasing global concern.

Despite an increasing incidence of acute kidney injury in both high-income and low-income countries and growing insight into the causes and mechanisms of disease, few preventive and therapeutic options exist. Even small acute changes in kidney function can result in short-term and long-term complications, including chronic kidney disease, end-stage renal disease, and death. Presence of more than one comorbidity results in high severity of illness scores in all medical settings. Development or progression of chronic kidney disease after one or more episode of acute kidney injury could have striking socioeconomic and public health outcomes for all countries. Concerted international action encompassing many medical disciplines is needed to aid early recognition and management of acute kidney injury.

How to use biomarkers efficiently in acute kidney injury.

We discuss the performance of novel biomarkers in acute kidney injury (AKI). Comparison of the areas under the receiver operating characteristic curves of several biomarkers with some clinical and/or routine biochemical outcome parameters reveals that none of the biomarkers has demonstrated a clear additional value beyond the traditional approach in clinical decision making in patients with AKI. Unscrutinized use of these biomarkers may distract from adequate clinical evaluation and carries the risk of worse instead of better patient outcome.

Clinical practice guidelines for anemia in chronic kidney disease: problems and solutions. A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).

The development of clinical practice guidelines for the treatment of anemia in chronic kidney disease has been instrumental in identifying and reducing variations in the use of erythropoiesis-stimulating agents and iron replacement. Challenges to the effectiveness and safety of recommendations made in these guidelines were magnified when recent clinical trials showed no benefit or harm with respect to cardiovascular outcomes in subjects randomized to higher target hemoglobin levels. To address these concerns, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international conference to examine the problems and shortcomings of existing anemia guidelines, which are a prime example of duplication of efforts to derive recommendations from a limited evidence base. The meeting was attended by representatives of the major guideline developing organizations, who agreed to avoid future duplicative efforts and to save resources in generating a common evidence report, whose recommendations could then be prioritized and implemented locally. This is a report to the international nephrology community of the recommendations for and timeline of the next anemia guidelines. It has been reviewed by the conference participants and approved as a position statement by the KDIGO Board of Directors.

Health implications of antimicrobial resistance for patients with acute kidney injury and bloodstream infection.

Studies have produced conflicting findings on outcomes for patients with antimicrobial-resistant infection. This study evaluated whether infection with an antimicrobial-resistant organism affects outcome in critically ill patients with acute kidney injury treated with renal replacement therapy and whose clinical course is complicated with a nosocomial bloodstream infection. We found that infection with an antimicrobial-resistant organism did not adversely affect clinical outcome in this specific cohort, which already has a high mortality rate.

Endothelium-derived hyperpolarizing factor-mediated renal vasodilatory response is impaired during acute and chronic hyperhomocysteinemia.

BACKGROUND: Endothelial dysfunction is an early event in the development of vascular complications in hyperhomocysteinemia. Endothelial cells release a number of vasodilators, including NO and prostacyclin. Several lines of evidence have indicated the existence of a third vasodilator pathway, mediated by endothelium-derived hyperpolarizing factor (EDHF). EDHF is a major determinant of vascular tone in small resistance vessels. The influence of hyperhomocysteinemia on EDHF is unknown. The present in vivo study evaluates the integrity of the EDHF pathway in the renal microcirculation of rats with acute and chronic hyperhomocysteinemia. METHODS AND RESULTS: EDHF-mediated vasodilation was evaluated as the renal blood flow (RBF) response to intrarenal acetylcholine during systemic NO synthase and cyclooxygenase inhibition. Acute hyperhomocysteinemia induced by intravenous homocysteine did not affect EDHF-mediated vasodilation. In contrast, intravenous methionine with subsequent hyperhomocysteinemia impaired the EDHF-mediated RBF response. When the methionine infusion was preceded by adenosine periodate oxidized to prevent the cleavage of S-adenosylhomocysteine to homocysteine and adenosine, a similar impairment of EDHF was observed, but with normal homocysteine levels. Animals with chronic hyperhomocysteinemia induced by a high-methionine, low-B vitamin diet during 8 weeks had a severely depressed EDHF-mediated vasodilation compared with those on a standard diet. Endothelium-independent vasodilation to deta-NONOate and pinacidil was not affected in acute and chronic hyperhomocysteinemia, demonstrating intact vascular smooth muscle reactivity. CONCLUSIONS: EDHF-dependent responses are impaired in the kidney of hyperhomocysteinemic rats. Because EDHF is a major regulator of vascular function in small vessels, these findings have important implications for the development of microangiopathy in hyperhomocysteinemia.

Pathophysiological role of vascular endothelial growth factor in the remnant kidney.

BACKGROUND: Subtotal renal ablation is characterized by initial glomerular hypertrophy, followed by progressive development of glomerulosclerosis and interstitial fibrosis. Vascular endothelial growth factor (VEGF) is involved in glomerular hypertrophy and dysfunction in several pathophysiological conditions. On the other hand, progressive glomerulosclerosis and tubulo-interstitial fibrosis in the remnant kidney have been associated with loss of VEGF expression. METHODS: To explore the pathophysiological role of VEGF in the development of glomerular hypertrophy and renal damage in the remnant kidney model, we examined the effect of a neutralizing VEGF antibody on glomerular volume and kidney function in rats after subtotal nephrectomy or sham operation. Erythropoietin was administered to exclude a confounding effect of anaemia. RESULTS: Six weeks after subtotal nephrectomy, plasma urea and creatinine concentrations, urinary albumin excretion, and mean glomerular volume were elevated in the placebo-treated uraemic rats as compared with the sham-operated rats. Inhibition of VEGF partially prevented the glomerular hypertrophy and largely prevented the rise in urinary albumin excretion, but did not affect creatinine clearance in uraemic rats. CONCLUSIONS: VEGF is a mediator of glomerular hypertrophy after subtotal renal ablation. In view of glomerular hypertrophy as the initial deleterious event ultimately leading to progressive glomerulosclerosis, agents that block this glomerular growth could be useful in preventing scarring in progressive renal disease.

Sodium bicarbonate versus THAM in ICU patients with mild metabolic acidosis.

BACKGROUND: Sodium bicarbonate is despite its side effects, considered the standard alkali therapy in metabolic acidosis. THAM is an alternative alkalizing agent; however, there are limited data on the use of THAM in metabolic acidosis. The aim of this study was to compare the efficacy and adverse effects of a single dose of sodium bicarbonate and THAM in intensive care unit (ICU) patients with mild metabolic acidosis. METHODS: 18 adult ICU patients with mild metabolic acidosis (serum bicarbonate < 20 mmol/L) were randomized to a single dose of either sodium bicarbonate or THAM, administered over a 1-hour period, and titrated to buffer the excess of acid load. RESULTS: Sodium bicarbonate and THAM had equivalent alkalinizing effect during the infusion period. This was still present 4 hours after start of infusion of sodium bicarbonate, and until 3 hours after start of infusion of THAM. Serum potassium levels decreased after sodium bicarbonate infusion, and remained unchanged after THAM. After sodium bicarbonate, sodium increased, and after THAM, serum sodium decreased. CONCLUSIONS: Sodium bicarbonate and THAM had a similar alkalinizing effect in patients with mild metabolic acidosis; however, the effect of sodium bicarbonate was longer lasting. Sodium bicarbonate did decrease serum potassium, and THAM did not; THAM is therefore not recommended in patient with hyperkalemia. As sodium bicarbonate leads to an increase of serum sodium and THAM to a decrease, THAM may be the alkalinizing agent of choice in patients with hypernatremia. Similarly, because sodium bicarbonate increases PaCO2 and THAM may even decrease PaCO2, sodium bicarbonate is contraindicated and THAM preferred in patients with mixed acidosis with high PaCO2 levels.

Animal models in peritoneal dialysis research: a need for consensus.

The development of an adequate animal model for peritoneal research remains an object of concern. In vivo peritoneal dialysis (PD) research is hampered by the large variety of available models that make interpretation of results and comparison of studies very difficult. Species and strain of experimental animals, method of peritoneal access, study duration, measures of solute transport and ultrafiltration, and sampling for histology differ substantially among the various research groups. A collective effort to discuss the shortcomings and merits of the different experimental models may lead to a consensus on a standardized animal model of PD.

Anemia management for hemodialysis patients: Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines and Dialysis Outcomes and Practice Patterns Study (DOPPS) findings.

BACKGROUND: After recombinant human erythropoietin was introduced into routine nephrologic practice, specific clinical guidelines were developed to optimize the quality of anemia management for patients with chronic kidney disease. METHODS: The Dialysis Outcomes and Practice Patterns Study (DOPPS), an international investigation providing patient- and facility-level data on hemodialysis practice, was developed to provide information on various aspects of current practices in hemodialysis management, including treatment of renal anemia. RESULTS: Hemoglobin concentration is strongly associated with both morbidity and mortality in hemodialysis patients. Although some improvements can be documented in anemia management practices in the years after the publication of international guidelines, wide variations in anemia management are still observed among countries. CONCLUSION: Many efforts are still needed to allow a greater proportion of patients to reach the recommended hemoglobin concentrations. Significantly improved outcomes may therefore be expected by a more widespread reaching of the recommended hemoglobin levels. The results of the DOPPS point to the difficulties in implementing clinical guidelines in the everyday management of individual patients. In specific circumstances, a well-designed observational study may offer credible information and serve as a basic instrument for monitoring the implementation of clinical guidelines in typical clinical practice.

Serum cystatin C concentration compared with other markers of glomerular filtration rate in the old old.

OBJECTIVES: To assess serum cystatin C, compared with other markers of renal function, as a marker of renal function in the old old (aged 85 and older). DESIGN: A cross-sectional analysis of data obtained in medically stable people aged 70 and older in a geriatric ward at a university hospital. SETTING: University hospital in Belgium. PARTICIPANTS: Forty-eight patients (17 men, 31 women) mean age +/- standard deviation 84.4 +/- 6.3 without acute illness or overt malignancy 7 days after admission were included. Twenty-five patients were aged 85 and older. MEASUREMENTS: Blood samples and 24-hour urine collections were obtained from each patient to determine serum creatinine, serum cystatin C levels, serum albumin, and creatinine clearance. Glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault formula and the Modification of Diet in Renal Study Group (MDRD) formula. On the same day, clearance of 51chromium ethylenediamine tetraacetic acid was performed in all patients as the criterion standard of GFR. RESULTS: Serum creatinine (r=0.68), serum cystatin C (r=0.62), urinary creatinine clearance (r=0.57), the Cockcroft-Gault formula (r=0.82), and the MDRD-formula (r=0.65) correlated significantly with GFR (P <.0001). Regression analysis showed that serum cystatin C and serum creatinine were comparable markers of renal function (Y=0.442 +/- 0.007 x GFR and Y=0.494 +/- 0.01 x GFR respectively). Receiver operating characteristic analysis showed a similar area under the curve for serum cystatin C and serum creatinine (P=.5) in detecting renal impairment (GFR <80 mL/min). The Cockcroft-Gault formula provides a good estimation of GFR when the GFR is less than 60 mL/min (Y=1.11 +/- 1.04 x GFR). When the GFR is greater than 60 mL/min, the Cockcroft-Gault formula underestimates GFR (Y=11.01 +/- 0.66 x GFR). In patients aged 85 and older, a slight decrease in GFR (51.8 +/- 21.3 mL/min vs 65.2 +/- 34.3 mL/min in patients aged 70-84; P=.10) is observed. This is reflected by a nonsignificant increase in serum cystatin C (P=.06), whereas serum creatinine is identical in both groups (P=.88). CONCLUSION: Serum cystatin C, serum creatinine, the Cockcroft-Gault formula, the MDRD formula, and urinary creatinine clearance are comparable markers of renal function in the overall older population. The Cockcroft-Gault formula underestimates renal function in older people with GFR greater than 60 mL/min. In our study, serum cystatin C was not superior to serum creatinine in the detection of renal impairment.

Vascular hyporesponsiveness in the mesenteric artery of anaesthetized rats with cirrhosis and portal hypertension: an in-vivo study.

INTRODUCTION: Cirrhosis is complicated by splanchnic vasodilation. Nitric oxide (NO) and prostacyclin contribute to this. Vascular hyporesponsiveness has been reported, but the underlying pathophysiological mechanisms are unclear. OBJECTIVE: This in-vivo study examined the contribution of NO and prostacyclin to the development of vascular hyporesponsiveness in the mesenteric circulation of animals with cirrhosis and portal hypertension. METHODS: Rats underwent common bile duct ligation (CBDL) (n = 11), partial portal vein ligation (PPVL) (n = 12) and sham-operation (sham) (n = 11). Blood flow in the mesenteric artery (MBF) was measured during intramesenteric infusion of endothelium-dependent (acetylcholine) and endothelium-independent vasodilators (deta-NONOate, pinacidil) and a vasoconstrictor (L-phenylephrine). The measurements were repeated after systemic infusion of L-NAME (NO synthase inhibition) and indomethacin (cyclo-oxygenase inhibition). RESULTS: The MBF response to acetylcholine was significantly lower in CBDL and tended to be lower in PPVL than in sham. L-NAME and indomethacin significantly decreased the MBF response to acetylcholine in all groups. The hyporeactivity to acetylcholine in CBDL and PPVL was maintained after L-NAME and indomethacin. The MBF response to pinacidil, deta-NONOate and phenylephrine, before and after NO synthase and cyclo-oxygenase inhibition, was lower in CBDL and PPVL than in sham. CONCLUSION: This is the first in-vivo study demonstrating an impaired response to endothelium-dependent and endothelium-independent vasodilators as well as vasoconstrictors in the mesenteric artery of animals with cirrhosis and portal hypertension. The generalised hyporeactivity suggests an abnormality on the vascular smooth muscle cell level. The hyporesponsiveness persisted after combined NO synthase and cyclo-oxygenase inhibition.

Effect of dietary creatine on skeletal muscle myosin heavy chain isoform expression in an animal model of uremia.

BACKGROUND: Chronic renal failure is accompanied with muscle dysfunction and myopathy, characterized by muscle weakness and increased fatigue. Myosin heavy chain (MHC) is the principal structural protein that controls the intrinsic contractile properties of striated muscle. Creatine is widely used as an ergogenic nutritional supplement in sportsmen. This study investigates the effect of creatine supplementation on MHC expression in the setting of uremic myopathy. METHODS: Male Wistar rats were either sham operated or subtotally nephrectomized and received a control diet or creatine (2% w/w)-supplemented diet. After 4 weeks of treatment, serum creatinine, creatine, urea and creatinine clearances were determined. MHC isoforms were determined electrophoretically in the extensor digitorum longus and soleus muscles. RESULTS: Creatinine clearances were lower in nephrectomized animals, but similar in creatine-supplemented and control diet animals. Nephrectomized animals had significantly higher MHC IIb and lower MHC IIx isoform expression in the extensor digitorum longus muscle compared to sham-operated animals. In the soleus muscle, MHC IIb expression was increased in nephrectomized animals. Creatine supplementation reversed the MHC transitions observed in uremia in the soleus muscle, but not in the extensor digitorum longus muscle. CONCLUSION: We observed altered expression of MHC isoforms in uremia. In uremic animals, fast MHC IIb isoforms were increased, whereas MHC I and IIx isoforms predominate in control animals. Dietary creatine supplementation reversed the altered MHC expression during uremia in slow-twitch, but not in fast-twitch muscles.

The effects of peritoneal dialysis solutions on peritoneal host defense.

Conventional peritoneal dialysis fluid (PDF) is a bioincompatible solution owing to the acidic pH, the high glucose concentrations and the associated hyperosmolarity, the high lactate concentrations, and the presence of glucose degradation products (GDPs). This unphysiologic composition adversely affects peritoneal host defense and may thus contribute to the development of PD-related peritonitis. The viability of polymorphonuclear leukocytes, monocytes, peritoneal macrophages, and mesothelial cells is severely depressed in the presence of conventional PDF. In addition, the production of inflammatory cytokines and chemoattractants by these cells is markedly affected by conventional PDF. Further, conventional PDF hampers the recruitment of circulating leukocytes in response to an infectious stimulus. Finally, phagocytosis, respiratory burst, and bacterial killing are markedly lower when polymorphonuclear leukocytes, monocytes, and peritoneal macrophages are exposed to conventional PDF. Although there are a few discrepant results, all major PDF components have been implicated as causative factors. Generally, novel PDF with alternative osmotic agents or with alternative buffers, neutral pH, and low GDP content have much milder inhibitory effects on peritoneal host defense. Clinical studies, however, still need to demonstrate their superiority with respect to the incidence of PD-related peritonitis.

Influence of dialysate on gastric emptying time in peritoneal dialysis patients.

OBJECTIVE: Peritoneal dialysis (PD) patients frequently suffer from dyspeptic complaints such as nausea, vomiting, abdominal distension, early satiety, and anorexia. Gastroparesis might be, at least partially, a source of dyspeptic complaints in PD patients. The aim of the present study was to determine the influence of the presence and composition of dialysate on gastric emptying in PD patients. DESIGN: Prospective study. SETTING: Renal Division, Department of Internal Medicine, Ghent University Hospital, Belgium. PATIENTS: Sixty-one PD patients using different dialysate solutions, and 27 healthy volunteers. MAIN OUTCOME MEASURE: Gastric emptying of solids was assessed by the 13C-octanoic acid breath test. RESULTS: Gastric emptying was impaired in PD patients, regardless of the composition of dialysate and even if tested with an empty peritoneal cavity. Gastric emptying was significantly slower when glucose-containing dialysate was compared to an empty peritoneal cavity, or when glucose-containing dialysate was compared to icodextrin dialysate. No difference in gastric emptying could be demonstrated between glucose-containing dialysate and dialysate containing a mixture of glycerol and amino acids as osmotic agent. CONCLUSIONS: These findings suggest that the delay in gastric emptying demonstrated in the presence of peritoneal dialysate is not the consequence of a mere volume or pressure effect, but of the absorption of substrate substances with caloric and/or metabolic activity, such as glucose or glycerol and amino acids.

Antibiotic administration in an animal model of chronic peritoneal dialysate exposure.

OBJECTIVES: The high incidence of intraperitoneal infection remains an important problem in animal models of chronic dialysate exposure. Prophylactic antibiotic administration can be used to resolve this problem, but the isolated effects of antibiotics on peritoneal membrane function and structure are unknown. The present study examined the effects of prophylactic antibiotics on infection rate and peritoneal membrane function and structure in a rat model of chronic dialysate exposure. DESIGN: A first group of rats (A; n = 12) received 10 mL 3.86% glucose dialysate twice daily through a heparin-coated catheter. In a second group of animals (B; n = 12), oxacillin 2.5 mg/day and gentamicin 0.04 mg/day were added to the dialysate. Group C (n = 12) was injected twice daily with an identical dose of antibiotics dissolved in 1 mL of buffer solution. Group D (n = 12) was left untreated. Dialysate cultures were obtained regularly. After 8 weeks of exposure, peritoneal transport studies were performed and samples for histology were obtained. RESULTS: Technique survival was 92% in group A and 100% in the remaining groups. Five rats in group A but none of the animals in the other groups developed peritonitis. The transport rates of small solutes were elevated and net ultrafiltration was decreased in group A compared to the controls. Fibrosis, as evaluated by quantifying Picro Sirius Red staining with image analysis, was significantly elevated in group A (3.48% +/- 1.06% vs 0.72% +/- 0.51% in group D, p < 0.05) but not in group B (0.29% +/- 0.07%) or in group C (0.52% +/- 0.28%). Vascular density, measured by counting the number of blood vessels that stained positive for endothelial NO synthase, was increased in both groups that were exposed to dialysate: 153.0 +/- 12.9/microm2 in group A and 131.6 +/- 14.3/microm2 in group B, versus 76.76 +/- 12.37/microm2 in group C and 73.2 +/- 10.4/microm2 in group D (p < 0.01). CONCLUSIONS: Prophylactic administration of oxacillin and gentamicin adequately prevented intraperitoneal infection in an animal model of chronic dialysate exposure. In addition, fibrosis was absent, suggesting intraperitoneal infection rather than dialysate exposure is a causative factor.

Comparison of the radioiodinated serum albumin (RISA) dilution technique with direct volumetric measurements in animal models of peritoneal dialysis.

BACKGROUND: Rat models of peritoneal dialysis (PD) are useful for studying the physiology of peritoneal transport and evaluating new osmotic agents. Intraperitoneal (IP) solute concentrations and their evolution over time are easy to measure, but IP volume (IPV) is not. Direct volumetric measurements are the "gold standard:" but they are expensive and do not allow for repetitive measurements in the same animal. The Indicator dilution technique is therefore used as an alternative. However, that technique is based on assumptions that are not always valid. The present study compares direct volume measurement with the Indicator dilution technique [radioiodinated serum albumin (RISA)] to determine the IPV over time curves In a rat model of PD. METHODS: In series 1, 17 Sprague-Dawley rats were instilled IP with 25 mL 1.36% glucose dialysate through a Teflon catheter. In 9 animals, 0.35 mL dialysate was sampled and discarded at time points 0, 3,15, 30, 60, 180, and 240 minutes. In the other 8 animals, no sampling was performed. At 240 minutes, all 12 animals were humanely killed, and direct volumetric measurements of IPV were performed. In series 2, rats were instilled IP with 25 mL 1.36% glucose dialysate containing 18.5 kBq 1311 RISA. In 9 animals, dialysate was sampled at 0, 3, 15, 30, 60, 90, 120,180, and 240 minutes for the construction of the RISA concentration-over-time curve, and to calculate the elimination constant Ke. At 30, 60, 180, and 240 minutes, dialysate was sampled in 6 different animals (total n = 24) to calculate IPV using the RISA dilution technique. Immediately afterward, the animals were humanely killed, and direct volumetric measurements of IPV were performed. RESULTS: In series 1, after 240 minutes' dwell time, the IPV was lower in the sampled animals as compared with the non sampled animals (27.11 +/- 1.85 mL vs 30.75 +/- 0.59 mL, p = 0.001). In series 2, the evolution of RISA activity in the dialysate over time was described by piecewise linear regression, yielding 3,288--8.2T counts (cts) for T < 52.72 minutes and 2,973--1.99T counts for T > 52.72 minutes. The IPV was better predicted with a Ke that took into account the disappearance of RISA by sampling than with a Ke that took into account disappearance of RISA only by absorption. CONCLUSIONS: If indicator dilution techniques are used to measure IPV, attention must be paid to the disappearance of the osmotic agent and the marker by multiple sampling. The best way to meet that goal is to use micropipettes to avoid large sample volumes.