- In observational studies, renal function as assessed by eGFR, albuminuria, urinary albumin-to-creatinine ratio, CKD, or ESRD yielded insufficient direct evidence for association with sodium intake.
- Five longitudinal studies did not generate robust evidence that reduction of salt intake would prevent CKD or its progression.
- The majority of intervention studies failed to provide sufficient information on design, results, and potential sources of bias, resulting in low quality scores.
- According to intervention studies, eGFR and albuminuria or proteinuria increased with higher salt intake.
Lithium, the cornerstone treatment for bipolar disorder, is associated with a decline in renal function, hypothyroidism, and hypercalcemia, new research suggests.
“Lithium is a widely used and highly effective treatment for mood disorders, but causes poorly characterized adverse effects in kidney and endocrine systems,” write investigators, led by Brian Shine, MD, from John Radcliffe Hospital, Oxford, United Kingdom. “We aimed to analyze laboratory information system data to determine the incidence of renal, thyroid, and parathyroid dysfunction associated with lithium use.”
The findings were published online May 20 in the Lancet.
For the study, the investigators extracted routinely collected data from the laboratory information system of the Clinical Biochemistry Department, Oxford University Hospitals National Health Service Trust.
The laboratory performs routine tests for primary and secondary care for about 650,000 people in Oxfordshire, United Kingdom, and surrounding counties and has been in continuous operation since 1985.
The study cohort included all patients aged 18 years or older who had had at least two creatinine, thyrotropin, calcium, glycated hemoglobin, or lithium measurements taken between October 1, 1985, and March 31, 2014.
The main exposure was lithium therapy, defined as more than two serum measurements in which lithium was detected. A total of 4678 patients had serum lithium concentrations measured once, and 60% of these (2795) had more than one measurement.
The remaining 689,228 patients in the cohort were matched for sex and age and served as nonexposed control participants.
The analysis showed that the presence of lithium in serum was strongly associated with a decline in renal function (estimated glomerular filtration rate <60 mL/min per 1.73 m2), hypothyroidism, and increased total serum calcium concentration, but not with hyperthyroidism or increased adjusted calcium concentration.
Table. Effects of Lithium on Renal and Endocrine Function
Function Hazard Ratio 95% Confidence Interval P-value
Stage 3 chronic kidney disease 1.93 1.76 – 2.12 < 0.0001
Hypothyroidism 2.31 2.05 – 2.60 < 0.0001
Increased total serum calcium concentration 1.43 1.21 – 1.69 < 0.0001
Hyperthyroidism 1.22 0.96 – 1.55 0.1
Increased adjusted calcium concentration 1.08 0.88 – 1.34 0.46
Young women had higher hazard ratios than other groups, which suggests they have the greatest risk for kidney disease and hypothyroidism.
The results also showed that the adverse effects occurred early in treatment and lessened with length of treatment (HR <1 for length of treatment with lithium). Higher than median lithium concentrations were associated with increased risk for all adverse outcomes.
The finding that length of lithium treatment has a negative association suggests that the onset of effects is rapid once patients start taking lithium, the authors write.
“All patients taking lithium therapy should have regular monitoring of renal function. The low risk of serious renal dysfunction should be balanced against the risks of the mood disorder and those of other mood stabilizers,” they add.
Because data for lithium dosing and renal risk are scarce, a “sensible” approach would be to minimize the dose of lithium used in general.
Patients receiving lithium should also undergo regular thyroid testing and have calcium levels measured at baseline and once a year thereafter, the authors advise.
They note that the strengths of their study are the large number of individuals and the length of follow-up, which, in many cases, was longer than 20 years.
The main limitations are the heterogeneity of the study population, the limited information on patients’ clinical features, not knowing why the specimens were taken, not knowing what proportion of patients taking lithium had bipolar vs unipolar disorder, and the lack of any information about the doses of lithium that were taken.
In an accompanying editorial, Gin S. Malhi, MD, from the University of Sydney, in Australia, writes that lithium is “without doubt the best treatment for many patients with bipolar disorder because it confers long-term mood stability and prophylaxi…reduces the risk of suicide and is possibly neuroprotective.”
Dr Malhi agrees with Dr Shine and colleagues that patients receiving lithium therapy should have their renal and thyroid function and blood calcium levels checked at the start of therapy and monitored closely thereafter.
“Maintenance of lithium concentrations at the lower end of the therapeutic range (ie, 0.6 mmol/L) can reduce the adverse outcomes associated with lithium treatment,” Dr Malhi writes.
However, acheiving blood concentrations of lithium high enough to be efficacious but low enough to avoid toxicity is a “delicate balance,” he writes.
“The dilemma of lithium therapy arises because, if poorly managed, lithium can compromise renal function, sometimes irreversibly, and severely disrupt endocrine homoeostasis — ultimately limiting its usefulness. Therefore, lithium therapy remains a challenge that will benefit from a better understanding of its therapeutic properties,” Dr Malhi writes.
Individuals with poor kidney function may require more intensive screening for these cancer types
Reduced kidney function may increase the risk of developing kidney and urothelial cancers, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings suggest that patients with kidney disease may benefit from more intensive screenings for these types of cancer.
Chronic kidney disease and cancer are both major and growing public health problems. “While multiple studies have observed higher risks of cancer in persons with end-stage renal disease, the association of less severe kidney disease with cancer remains poorly understood,” said Alan Go, MD (Kaiser Permanente Northern California).
To investigate, Dr. Go and his colleagues analyzed information from nearly 1.2 million adult members of Kaiser Permanente in Northern California who were at least 40 years of age and who had no history of cancer, dialysis, or kidney transplantation. Kidney function was measured by estimated glomerular filtration rate (eGFR), with normal kidney function being over 60 ml/min/1.73m2 and kidney failure being below 15 ml/min/1.73m2.
During more than 6 million person-years of follow-up, 72,875 individuals developed cancer. (A person-year is the number of years of follow-up multiplied by the number of people in the study.) Among the major findings during follow-up:
Individuals with an eGFR of 45 to 59 had a 39% increased risk of kidney cancer (or renal cell carcinoma).
Individuals with an eGFR of 30 to 44 had an 81% increased risk of kidney cancer.
Individuals with an eGFR below 30 had a 100% (or a 2-fold) increased risk of kidney cancer.
Individuals with an eGFR below 30 had a 48% increased risk of urothelial cancer, which includes tumors in the bladder and ureters.
There were no significant links between eGFR and other cancer types such as prostate, breast, lung, and colorectal cancers.
The researchers noted that various biologic mechanisms may help to explain the links observed in this study. For example, kidney dysfunction causes a state of chronic inflammation and oxidative stress. “These and other mechanisms deserve further study in order to better define the link between kidney function and site-specific cancer risk,” said lead author Will Lowrance, MD, MPH (University of Utah).
In an accompanying editorial, Jonathan Hofmann, PhD and Mark Purdue, PhD (National Cancer Institute) noted that the study is “an important step forward in characterizing the relationship between chronic kidney disease and risk of renal cell carcinoma and other malignancies. Studies such as this further support an etiologic role of impaired renal function in the development of renal cell carcinoma.”
Methods: In this observational study, we compared the estimated glomerular filtration rate (GFR) with poor 3-month outcome (modified Rankin Scale scores 3–6), death, and symptomatic intracranial hemorrhage (sICH) based on the criteria of the European Cooperative Acute Stroke Study II trial. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Patients without IVT treatment served as a comparison group.
Results: Among 4,780 IVT-treated patients, 1,217 (25.5%) had a low GFR (<60 mL/min/1.73 m2). A GFR decrease by 10 mL/min/1.73 m2 increased the risk of poor outcome (OR [95% CI]): (ORunadjusted 1.20 [1.17–1.24]; ORadjusted 1.05 [1.01–1.09]), death (ORunadjusted 1.33 [1.28–1.38]; ORadjusted 1.18 [1.11–1.249]), and sICH (ORunadjusted 1.15 [1.01–1.22]; ORadjusted 1.11 [1.04–1.20]). Low GFR was independently associated with poor 3-month outcome (ORadjusted 1.32 [1.10–1.58]), death (ORadjusted 1.73 [1.39–2.14]), and sICH (ORadjusted 1.64 [1.21–2.23]) compared with normal GFR (60–120 mL/min/1.73 m2). Low GFR (ORadjusted 1.64 [1.21–2.23]) and stroke severity (ORadjusted 1.05 [1.03–1.07]) independently determined sICH. Compared with patients who did not receive IVT, treatment with IVT in patients with low GFR was associated with poor outcome (ORadjusted 1.79 [1.41–2.25]), and with favorable outcome in those with normal GFR (ORadjusted 0.77 [0.63–0.94]).
Conclusion: Renal function significantly modified outcome and complication rates in IVT-treated stroke patients. Lower GFR might be a better risk indicator for sICH than age. A decrease of GFR by 10 mL/min/1.73 m2 seems to have a similar impact on the risk of death or sICH as a 1-point-higher NIH Stroke Scale score measuring stroke severity.
- Source: American Academy of Neurology
CT angiography (CTA) using moderate doses of IV contrast in patients with advanced renal failure is a safe procedure that negatively affects renal function in only a small percentage of patients, according to researchers from Baltimore.
But the imaging options are even better with newer MDCT scanners. CTA protocols with low kVp and using half the normal dose of iodinated contrast have even less impact on kidney patients and produce excellent images, said Dr. Barry Daly from the University of Maryland.
In a study presented at last month’s International Society for Computed Tomography (ISCT) meeting in San Francisco, Daly showed how even normal contrast doses had little effect on serum creatinine levels in most patients. Information gained by the studies far outweighs the chance of adverse effects in patients with chronic renal failure, he said.
Daly also showed his latest protocol for low-contrast-dose, low-kV CTA imaging that delivers high image quality with even less risk for these patients.
Don’t skip the CTA
CTA isn’t something you want to skip, even though many centers do just that, he said. Before renal transplant surgery, for example, surgeons need to see what they’re going to be dealing with in the operating room.
“There are big risks going into surgery without CTA in this group because they have the risk of a major change in operative procedure, prolonged surgery, poor graft outcomes, failure to engraft, loss of the organ — which is a total disaster, especially in the setting of matched renal donor transplantation — and, of course, the possibility of missing important pathologies,” Daly said.
|Patient is in renal failure but not yet on dialysis. CTA was acquired at 80 kVp and 360 mAs following administration of 50 mL of 350 mg/mL contrast. Contrast density in the iliac arteries is > 400 HU. Radiation dose is 4.3 mSv. There is an incidental right iliac venous stent. Images courtesy of Dr. Barry Daly.|
Daly and colleagues reviewed the use of CTA in 180 potential renal transplant recipients, all with matched donors, “but we were especially interested in looking at a predialysis cohort of 40 patients,” he said.
Patients were assessed for aortoiliac and calcific atherosclerosis, venous thrombosis, and increased incidence of renal cell carcinoma (four to seven times the normal rate in native kidneys). The only prophylaxis was aggressive oral hydration both before and after CTA, he said.
It’s important to find an appropriate place for the engraftment, Daly said. Many patients may require surgical correction with bypass grafts before transplantation can be done.
“Because a lot of these folks have had chronic hemodialysis, it’s not uncommon to find occlusion of the iliac veins,” he said. In a couple of cases, this has become obvious only in the operating room — “with disastrous consequences.”
The study measured serum creatinine (SeCr) and estimated glomerular filtration rate (eGFR) before and after imaging in the 40 predialysis patients. “There was almost no difference between the two groups in mean measurements,” Daly said.
“Nobody had to undergo dialysis, but looking at the changes, there clearly were some shifts that we shouldn’t ignore,” he said.
Post CTA, 27 patients had stable or mean decreased SeCr of 10.2%. Thirteen patients had a mean increase of 6.3%, with one patient showing a 32% rise, and three saw almost no change (0.5-1.5 mg/dL increase).
|Change in SeCr after CTA in predialysis cohort of 40 patients
A low rate of contrast-induced nephropathy (CIN) in renal patients isn’t all that surprising, Daly said. Newhouse, Katzberg, and others have shown that the risks of IV low-osmolar contrast precipitating CIN have been overestimated.
These previous studies demonstrate that moderate doses of IV contrast are much less nephrotoxic than arterial administration, he said. Many studies without controls failed to allow for other factors affecting renal function, especially in hospital populations. Finally, a 2010 study in Radiologyshowed that low-osmolar contrast may be as safe as iso-osmolar contrast, he noted.
Low-kVp, low-contrast-dose CTA
Daly and colleagues also performed a study of low-kVp, low-contrast-dose CTA in chronic renal failure patients. Why is this necessary if the regular dose is safe?
“The answer, of course, is that lower is always better,” Daly said. Even if the negative effects aren’t as bad as they were feared to be, “there is still a small portion of patients in our group who are still at risk with the conventional dose,” he said, adding that “new CT scanners have enabled new techniques for getting more out of each gram of iodine.”
The technique involves dropping the kV and increasing the mAs. For example, if you drop the tube current from 120 kV to 80 kV, you would increase the mAs by a factor of 2.7. Thus, 120 kVp and 250 mAs become 80 kV and 600 mAs, he said, and for large patients the tube may reach the maximum mAs.
MDCT can be used with extended z-axis coverage to shorten scan times to correspond to a shorter bolus train. Ideally, there should be at least 40 mm to 80 mm of coverage, he advised.
How it works is by now well-known, he said. “The k-edge of iodine is only [33.2] keV, so by dropping our kVp we can actually get considerably increased x-ray absorption. There’s a nearly a twofold increase in iodine attenuation at 80 kV compared to 120 kV.” Thus, the iodine dose can be cut in half while producing similar CT values, according to Daly.
The researchers perform the 80-kV studies on a Brilliance iCT 256 or a Brilliance 64 scanner (Philips Healthcare) using 320 to 350 mgI/mL of contrast.
They inject 35 to 50 mL of contrast at 4 mL per second in a peripheral vein, followed by 40 to 60 mL of a saline chaser at 4 mL per second. Automated bolus tracking is set for a 120- to 150-HU threshold in the aorta just below the hiatus, and the automated minimum scan delay is set to 4.2 to 6.5 seconds, he said.
Tube rotation speed is 0.75 seconds for a 256-slice scanner and 0.75 to 1 second for a 64-detector-row scanner. mAs values are based on patient body mass index (noise present at precontrast phase) with pitch set at maximum for the mAs selected, Daly said.
The resulting images look great, but using iterative reconstruction (iDose5, Philips) allows even lower doses, or the scanning of larger patients using low-kV, low-contrast protocols, he said.
In summary, CTA with a moderate 100-mL dose of iso-osmolar contrast in advanced renal failure “is a safe procedure with a negative impact on renal function in only a small percentage of patients,” Daly said, adding that “these aren’t patients with creatinine of 1.8, these are patients with major renal compromise.”
However, even though the 100-mL contrast protocol has a “very limited negative effect on people … a better option today is low 80-kVp, low-contrast-dose CTA technique with 35 to 50 mL of iso-osmolar contrast,” Daly said.
This very safe technique yields high diagnostic quality and works on most newer CT scanners, he added.
“Finally, if you have the benefit of iterative reconstruction, it improves image quality and allows us to use this technique even in very large patients,” Daly said.
Even patients with advanced kidney disease can steer clear of contrast-induced nephropathy (CIN) if given plenty of hydration, say researchers from the Netherlands. Results from the study of nearly 1,000 patients with stage 3 or 4 kidney disease were published in the June issue of Radiology.
The study found that fewer than 2.5% of the patients examined developed CIN when current guidelines emphasizing hydration were followed, according to the researchers from Radboud University Nijmegen Medical Centre in the Netherlands. The study also found that heart failure, low body mass index, and repeat contrast administration were associated with CIN.
CIN is the third most common cause of acute renal failure in hospitalized patients, and while most cases are limited to mild and transient impairment of renal function, serious morbidity and mortality, as well as longer hospital stays, can occur.
“In current practice, hydration is considered the preventive method of choice; however, evidence supporting its use is limited,” wrote Dr. Corinne Balemans and colleagues. Previous studies have relied on a variety of hydration protocols that were often used inconsistently (Radiology, June 2012, Vol. 263:3 pp. 706-713).
Balemans and colleagues aimed to determine risk factors associated with CIN by evaluating its incidence in patients with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 who received iodinated contrast media intravenously and were treated using current guidelines.
Current CIN guidelines developed in Europe and the U.S. emphasize the identification of patients at high risk for CIN and the use of hydration as a preventive measure, either using normal saline or sodium bicarbonate as an alternative option, they wrote.
In the study, patients with renal insufficiency were evaluated at a special outpatient clinic where CIN was assessed and normal saline hydration was prescribed (Centraal Begeleidings Orgaan guidelines, 2007), with renal function assessed after the procedures.
The researchers stratified all patients with eGFR less than 60 mL/min/1.73 m2 for risk of CIN; those at high risk based on absolute GFR and risk factors were hydrated with 1,000 mL of isotonic saline before and after contrast injection. Serum creatinine was measured three to five days later, and CIN was defined as an increase of 25% or more from baseline. Finally, the authors recorded and compared risk factors between patients with CIN and those without using stepwise multiple logistic regression analysis.
The study included 747 patients (43% female; mean age, 71.3 years ± 10) who underwent 944 procedures. Patients were hydrated in 511 (54.1%) procedures. CIN developed after 23 procedures (2.4%).
Independent predictors of CIN were heart failure (odds ratio, 3.0), body mass index (BMI) (odds ratio, 0.9), and repeated contrast material administration (odds ratio, 2.8), Balemans and colleagues wrote. No patients needed dialysis.
The population was carefully prepared before iodinated contrast injection, and only 7.7% of patients at high risk for CIN did not receive hydration.
“Our study provides reliable estimates of CIN and shows that the incidence of CIN is low in a homogeneous population of patients with stage 3 or 4 chronic kidney disease who underwent treatment in accordance with existing guidelines and who received intravenous iodinated contrast material,” the authors wrote.
In the study, money was saved by restricting hydration to about half of the study population; patients at high risk for CIN were hydrated, whereas those at low risk were not. However, it’s possible the incidence could have been reduced further by a less restrictive policy.
Regarding heart failure, a well-known risk factor for CIN, such patients may have more severe atherosclerotic vascular disease and are more prone to hemodynamic changes during and after procedures. For them, hydration may not be helpful, the authors wrote.
The inverse association between BMI and CIN may not have been reported previously, they noted. Patients with low BMI usually have a lower percentage of muscle mass, and as a result the formulas used to calculate eGFR overestimate renal function, Balemans and colleagues wrote.
Another study reported the association between repeat contrast exposure and CIN. In that study (Trivedi and Foley), the increased risk was even notable in patients with preserved renal function.
As for study limitations, the population was large but the number of events was small. Absolute GFR was used to classify risk, and there is debate about whether GFR should be corrected for body surface area.
The incidence of CIN in patients with stage 3 or 4 chronic kidney disease is low when treated in accordance with current guidelines, the authors concluded.
“Our findings support the efficacy of hydration regimens,” they wrote. “The risk of CIN is increased in patients with heart failure, low BMI, and repeated contrast material administration. These risk factors need to be validated in future studies.”
Cardiovascular disease is the main cause of death in patients with chronic kidney disease (CKD). Here we measured temporal trends in treatment and mortality after myocardial infarction (MI) depending on kidney function at presentation in 12,087 patients admitted for MI to a coronary care unit from 1985 to 2008. The patients were categorized into those with normal kidney function (estimated glomerular filtration rate over 90 ml/min per 1.73 m2), and those with CKD as defined by Kidney Foundation practice guidelines, with 8632 patients (71%) at CKD stages 2–5. Use of evidence-based care increased over time in all CKD stages. Mortality rates fell over the entire time period. When comparing data from 2000–2008 to that from 1985–1990, adjusted 30-day mortality fell both in patients with CKD stages 4–5 (adjusted odds 0.33, 95% confidence interval 0.18–0.60) and in those without kidney impairment (adjusted odds 0.21, 95% confidence interval 0.10–0.42). This mortality decrease was sustained during long-term follow-up. There was no significant interaction between kidney function and decade of admission. Overall, median survival was over 20, 15, 8, and 1.8 years for patients with normal kidney function, stage 2, stage 3, and stage 4–5 CKD, respectively. Thus, during the past 25 years, treatment of patients with a MI improved substantially with a concomitant decline in mortality. Although our findings were similar for all stages of kidney function, the prognosis remains poor for patients with stage 4–5 CKD.
|Despite early increases in acute kidney injury, invasive treatment is associated with better long-term outcomes than conservative management.|
|Invasive treatment options for acute coronary syndromes (ACS) might be underused in patients at high risk for renal disease because of concerns about contrast-induced renal failure and other complications. However, comparative data on renal outcomes in patients managed invasively versus conservatively are lacking. Therefore, investigators conducted a cohort study involving 10,516 patients presenting with non-ST-segment-elevation ACS in Alberta, Canada, 41% of whom received early invasive management (coronary catheterization within 2 days after hospital admission). Stratification according to baseline estimated glomerular filtration rate and propensity-score matching resulted in a cohort of 6768 participants.
Compared with conservative management, early invasive therapy was associated with an increased risk for acute renal injury (10.3% vs. 8.7%, P=0.019), but treatments did not differ in risk for dialysis (0.4% vs. 0.3%, P=0.670) during the index hospitalization. During a median follow-up of 2.5 years, the risk for progression to end-stage renal disease did not differ between the two groups (0.3 vs. 0.4 events per 100 person-years, P=0.712). Moreover, early invasive treatment was associated with reduced long-term mortality (2.4 vs. 3.4 events per 100 person-years; P<0.001). The relative reduction in mortality risk was consistent across all strata of baseline renal function.
Although early invasive treatment of acute coronary syndromes increased the risk for acute renal injury compared with conservative management, it did not affect risk for dialysis or progression to end-stage renal disease. The improvements in long-term survival at all levels of baseline renal function suggest that invasive therapy should not be withheld for fear of renal complications.
The contrast-induced nephropathy (CIN) is the third most common cause of acute renal failure (ARF) and the worsening in a pre-existing chronic renal failure (CRF), with a foreseeable increase of morbidity, mortality, length of the stay in hospital and, as a consequence, of the health costs. We studied the effectiveness of N-acetylcysteine (NAC) associated with sodium bicarbonate (Na2HCO3) infusion in order to prevent CIN in patients undergoing coronary angiography with administration of contrast medium.
MATERIALS AND METHODS:
296 patients with indication to perform coronary angiography were included in a randomized, observational study. All patients were randomly assigned to receive pre- and post-contrast hydration with 1500 ml of 0.9% saline solution infusion (Group A) or NAC (1200 mg × 2 days) + Na2HCO3 (Group B). The primary end-point was to examine CIN appearance, defined as a raise in serum values of Cr (Creatinine) ≥ 0.5 mg/dl or ≥ 25% within 24-72 hours after the exposure to the contrast medium.
It has been observed a frequency of CIN of 9.4% in Gr. A compared to 7.2% in Gr. B. Nevertheless, when we put these results through a more accurate screening according to gender, degree of raise in creatinine levels and the extent of change in GFR (glomerular filtration rate), we observed a very different behaviour. In patients with normal Cr and CrCl (Clearance of Creatinine) the frequency of CIN was similar in both group A and B (approximately 5%). In patients with normal Cr but reduced ClCr the use of NAC was more effective than hydration in preventing CIN (0% vs 18% in prevalence respectively in B and A group). In patients with moderately reduced Cr and CrCl, hydration with saline solution was more effective than NAC + Na2HCO3 (8.6% vs 17.6%) while in patients with severe CRF the combined use of NAC + Na2HCO3 showed off to be very successful in preventing CIN compared to the merely hydration (0% vs 50%).
In patients affected by severe CRF who are undergoing investigations with contrast medium administration, such as coronary angiography, the combined use of NAC + Na2HCO3 infusion significantly reduces the risk of developing CIN. In other circumstances the final result is related to the degree of previous GFR or creatinine values alteration or to gender. In such situations the combined use of both substances is more questionable and sometimes ineffective.
Lipid peroxidation impairs renal function. Aldosterone contributes to renal injury in the remnant kidney model. This study aimed to determine the effects of the antioxidant N-acetylcysteine (NAC) on renal function and aldosterone levels in chronic renal failure.
Adult male Wistar rats were submitted to 5/6 nephrectomy or laparotomy (sham-operated) and received NAC (600 mg/L in drinking water, initiated on postoperative day 7 or 60), spironolactone (1.5 g/kg of diet initiated on postoperative day 7), the NAC-spironolactone combination or no treatment. Clearance studies were performed on postoperative days 21, 60, and 120.
Mean daily NAC and spironolactone ingestion was comparable among the treated groups. Mean weight gain was higher in NAC-treated rats than in untreated rats. A significant decrease in urinary thiobarbituric acid reactive substances (TBARS) concentrations, a lipid peroxidation marker, was observed in NAC-treated rats. By day 120, glomerular filtration rate (GFR), which dropped dramatically in untreated rats, was stable (albeit below normal) in NAC-treated rats, which also presented lower proteinuria, glomerulosclerosis index, and blood pressure, together with attenuated cardiac and adrenal hypertrophy. These beneficial effects, observed even when NAC was initiated on postnephrectomy day 60, were accompanied by a significant reduction in plasma aldosterone and urinary sodium/potassium ratio. The NAC-spironolactone combination lowered blood pressure and improved GFR protection.
The NAC-spironolactone combination improves renal function more than does NAC alone. In the remnant kidney model, early or late NAC administration has a protective effect attributable to decreased plasma aldosterone and lower levels of lipid peroxidation.
Our data demonstrate that NAC attenuates drops in GFR, as well as lowering proteinuria and blood pressure in nephrectomized rats. This is accompanied by a significant reduction in aldosterone levels. Our results indicate that ROS play an important role in the progression of chronic renal failure. It is evident that NAC has potential utility in preventing glomerulosclerosis and loss of kidney function in patients with chronic renal failure. The findings that NAC attenuated GFR drop and lowered proteinuria, even in end-stage chronic renal failure, and that the combination of NAC and spironolactone improves renal function more than does NAC alone have significant clinical implications.
Source: Nature Kidney