One Stop Doc Gastroenterology and Renal Medicine

Please accept our apologies for any inconvenience this may cause. Exclusive web offer for individuals. Add to Wish List. Toggle navigation Additional Book Information. Description Table of Contents Author s Bio. Summary The One Stop Doc books have been designed by medical students for medical students to consolidate their knowledge, subject by subject and system by system. For each area studied there are only so many questions an examiner can ask; they are presented here with clear explanations that allow the student to revise thoroughly one topic at a time.

Other Authors Adebayo, Danielle. Series One stop doc One stop doc. Gastroenterology -- Problems, exercises, etc.

Kidneys -- Diseases -- Problems, exercises, etc. Summary The One Stop Doc books have been designed by medical students for medical students to consolidate knowledge, subject by subject and system by system. For each area studied there are only so many questions an examiner can ask; they are presented here with clear explanations that allow the student to revise thoroughly one topic at a time.

While doing so, the student can also practice their exam technique. Illustrated with simple, easy-to-reproduce line drawings. Contents Machine derived contents note: View online Borrow Buy Freely available Show 0 more links Related resource Table of contents only at http: Set up My libraries How do I set up "My libraries"? These 11 locations in All: John and Alison Kearney Library. Open to the public ; RC Open to the public Princess Alexandra Hospital Library. Mean half-life of exenatide was 1. The most common treatment-emergent adverse events were vomiting, nausea and headache.

1st Edition

Although the dose-normalized plasma maximum concentration and exposure of exenatide were greater in elderly patients, no statistically significant between-age group differences were observed. Transforming growth factor beta 1; GLP Glucagon-like peptide 1; T2DM: Type 2 diabetes mellitus; ESRD: End-stage renal disease; FDA: There are a number of case reports associating exenatide with the development of acute kidney injury[ 37 - 39 ].

The United States Food and Drug Administration FDA reported that between April and October there were 78 cases of altered kidney function 62 cases of acute renal failure and 16 cases of renal insufficiency with exenatide[ 32 ]. Also, there was incomplete recovery of kidney function in many patients. Some of these cases occurred in patients with pre-existing kidney disease. Ninety-five percent of the patients who experienced deterioration of kidney function had at least one risk factor for developing kidney problems, such as use of nephrotoxic medications, cardiac insufficiency or hypertension; these factors could have independently increased the risk for renal dysfunction[ 32 ].

In most reports the acute kidney injury seems to be due to exenatide-induced prerenal acute failure. Main side effects of exenatide administration are nausea and vomiting, which result in decreased fluid intake and a significant loss of fluids[ 40 ].

Upcoming Events

The resulting volume contraction may lead to acute renal failure. Effects of GLP-1 such as natriuresis and a possible decrease in renal perfusion may also play a role in the loss of fluids and impairment of renal function[ 41 , 42 ]. The exenatide-induced volume contraction is mainly seen in patients who receive drugs that inhibit the renin-angiotensin system and aldosterone formation, an important homeostatic mechanism in states associated with volume depletion[ 43 ].

• 100 General Knowledge Quiz Questions - March 2013.
• Bestselling Series?
• A Portrait of A Christian.

Furthermore, uremia per se is associated with nausea and may lead to a vicious circle of renal function deterioration[ 44 ]. In agreement with the above mechanisms, Weise et al[ 45 ] reported that four patients with nausea and vomiting experienced deterioration of kidney function following treatment with exenatide. There was incomplete recovery of kidney function in three patients. A kidney biopsy, which was performed in one patient, revealed ischemic glomeruli with moderate to severe interstitial fibrosis and early diabetic nephropathy[ 45 ].

It should also be mentioned that other mechanisms of exenatide-induced acute kidney injury have been reported. Treatment with exenatide was initially associated with significant loss of weight from 83 kg to 77 kg. However, after 2 mo an increase in serum creatinine concentration [from 1. He did not take any non-steroidal anti-inflammatory drugs or other non-prescribed medications. One month later, the serum creatinine concentration had increased to 2. There was further deterioration in his kidney function over the next month [ creatinine concentration 4. His urine contained red and white blood cells.

An ultrasound examination revealed two normal kidneys.

• Evaluation dans la formation des enseignants (Evaluer) (French Edition)!
• Friedmans Family Law (Friedmans Practice).
• One stop doc gastrolentrology and renal medicine.

There was no evidence of a skin rash and the full blood count was normal. A kidney biopsy revealed active, moderately severe diffuse tubulointerstitial nephritis. The inflammatory infiltrate included many eosinophils, implying a drug-induced reaction. There was active tubular damage with desquamation of epithelium. He was treated with prednisolone 50 mg daily and an improvement in kidney function was observed within a few days.

Prednisolone was gradually reduced over the next few weeks to a daily dose of 10 mg with a further improvement in kidney function [creatinine concentration 1. Similarly, in , Bhatti et al[ 47 ] reported that two patients had experienced deterioration in kidney function following treatment with exenatide. One patient had no clinical evidence of dehydration and no response to rehydration was seen.

This patient had hematuria and proteinuria and interstitial nephritis was suspected; however, a kidney biopsy was not performed. The patient was treated with prednisolone and there was incomplete recovery of kidney function. The other patient had clinical evidence of dehydration and there was improvement in kidney function following rehydration[ 47 ]. Furthermore, the once weekly exenatide, which was recently approved by the FDA, is not recommended in patients with severe renal impairment or ESRD and caution is warranted in patients with renal transplantation or moderate renal impairment[ 48 ].

However, it should be mentioned that the reported cases of altered renal function with exenatide represent a small percentage of the total number of patients who have used the drug more than 6. Furthermore, recent analyses do not associate exenatide use and acute kidney injury. Transient, mild-to-moderate nausea was the most frequent adverse event with exenatide Renal impairment-related adverse events, including acute renal failure, were low 1.

Additionally, a retrospective cohort study of a large medical and pharmacy claims database including data for patients was recently published[ 50 ]. The unadjusted incidence rates of acute kidney injury were higher in patients with T2DM 1. The unadjusted incidence rates of acute kidney injury were similar between exenatide users 0.

Effects of glucagon-like peptide-1 receptor agonists on renal function

Similar results were observed when analysis was restricted to the patients with at least one risk factor for acute kidney injury [ exenatide user: Effects on diabetic nephropathy: Diabetic nephropathy is histologically characterized by the accumulation of extracellular matrix proteins in the glomerular mesangium[ 51 ]. Treatment with exendin-4 improves the renal interstitial fibrosis in culture and animal models of diabetic nephropathy. A reduction in protein levels of intercellular adhesion molecule-1 and type IV collagen together with a decrease in macrophage infiltration, oxidative stress and nuclear factor- K B activation were also observed in the kidney tissue of diabetic rats[ 59 ].

Furthermore, there are other possible mechanisms that GLP-1 receptor agonists improve diabetic nephropathy.

Exendin-4 in vitro improved endothelium-dependent relaxation and restored renal blood flow in spontaneously hypertensive rat renal arteries and increased nitric oxide production in spontaneously hypertensive rat aortic endothelial cells[ 60 ]. Furthermore, ex vivo exendin-4 administration improved endothelial function of renal arteries from hypertensive patients. It seems that GLP-1 receptor agonists improve endothelial function by restoring nitric oxide bioavailability[ 60 ].

Other authors have shown that the protective action of GLP-1 in glomerular endothelial cells is partly mediated via its own receptor by the activation of protein kinase A[ 61 ]. In this context, exendin-4 has been described to exert anti-hypertensive effects through the attenuation of angiotensin II-mediated effects. Exendin-4 also prevented angiotensin II-induced hypertension in angiotensin II-infused non-diabetic mice[ 62 ]. Of note, a 2-h infusion of GLP-1 in 12 healthy young males was associated with a significant reduction of angiotensin II levels with no parallel change in the concentration of renin and aldosterone or the urinary excretion of angiotensinogen[ 63 ].

There is also evidence of a beneficial role of the combination of GLP-1 receptor agonists with angiotensin converting enzyme inhibitors. A peptide analogue with exenatide AC 1. It should be mentioned that the administration of GLP-1 did not result in improvement of cardiovascular parameters and survival, implying that GLP-1 receptor agonists are more potent peptides or have at least partly different mechanism of action[ 64 ]. Exenatide resulted in a significant reduction of body mass index BMI by 5.

Similar reductions of fasting plasma glucose and HbA1c were observed between the two groups. Additionally, the excretion of urinary type IV collagen was significantly decreased with exenatide Interestingly, a study showed that exenatide exerts protective effects on liver injury induced by renal ischemia reperfusion in diabetes[ 66 ]. Overall, GLP-1 receptor agonists seem to improve the histologic changes and markers of diabetic nephropathy.

These effects seem promising for the treatment of T2DM patients. However, it should be mentioned that most of the evidence is based on animal studies and the extrapolation of these observations to human physiology should be done with caution. Effects on water and electrolyte balance: GLP-1 receptors are expressed in the proximal tubule[ 68 ].

There is evidence from animal studies that GLP-1 modulates sodium homeostasis in the kidney via the GLP-1 receptor in proximal tubular cells. Specifically, GLP-1 administration in porcine proximal tubular kidney cells led to an inhibition of sodium re-absorption after 3 h of incubation. In contrast, the use of a DPP-IV inhibitor in combination with exendin-4 or GLP-1 did not alter significantly glucose and sodium uptake and transport[ 68 ]. It was also demonstrated that GLP-1 can stimulate renal excretion of sodium in rats and humans, most likely by affecting NHE3 activity[ 41 , 69 , 70 ].

It was also shown that GLP-1 significantly reduced NHE3-mediated bicarbonate reabsorption in rat renal proximal tubule, through a protein kinase A-dependent mechanism[ 71 ]. Another study reported that parenteral administration of exendin-4 in wild-type mice induced diuresis and natriuresis[ 72 ]. These effects were abolished in mice lacking the GLP-1 receptor and were independent of adenylate cyclase 6.

Of interest, the administration of parenteral DPP-IV inhibitor alogliptin in these wild-type mice induced diuresis and natriuresis, which were independent of the presence of the GLP-1 receptor or alterations in the phosphorylated NHE3. These results may imply mechanistic differences between exendin-4 and DPP-IV inhibition in the induction of diuresis and natriuresis under normal states.

• String Quartet No. 7 in D Major, D94 - Viola;
• ULTRAS (Yaoi Manga)!
• I Shall Not Die But, LIVE;
• One Stop Doc Gastroenterology and Renal Medicine;

A recent study described a role of exenatide as a proximal diuretic and renal vasodilator[ 73 ]. Furthermore, exenatide administration was associated with a significant increase of heart rate 8. These effects were not linked with any change in blood pressure levels[ 74 ]. Therefore, exenatide has both vasodilator and natriuretic properties.

Although the effects of short-time administration of exenatide were not associated with significant changes in blood pressure levels, they may be related with the reduction in blood pressure that was observed in clinical studies examining the use of GLP-1 receptor agonists in patients with T2DM[ 75 , 76 ]. Furthermore, a possible role of exenatide in the human osmoregulation system has been proposed.

A study article in Russian, so no more details than the abstract could be used showed that water load of 0. Finally, there is evidence of a possible role of exenatide in the normalization of potassium balance via renal mechanisms. The administration of exenatide 0. Moreover, exenatide enhanced excretion of potassium in Wistar rats with hyperkalemia produced by intraperitoneal injection of 1. A study in seven healthy males who received radio-labelled liraglutide showed that liraglutide is metabolized by DPP-IV and neutral endopeptidase, similarly with the native GLP-1 but at a much slower rate.

Furthermore, the results of this study showed that liraglutide is mainly degraded within the body since no intact liraglutide was excreted in urine and feces[ 82 ]. Renal impairment does not alter significantly the pharmacokinetic profile of liraglutide[ 33 ]. In a study a single dose of liraglutide 0. The regression analysis of log [area under the curve AUC ] of liraglutide for subjects with normal renal function and mild-to-severe renal impairment did not show any significant effect of reduced creatinine clearance on the pharmacokinetics of liraglutide.

Furthermore, the AUC ratio of the subject with the lowest and the subject with the highest creatinine clearance was not significant 0. However, no association was found between the degree of renal impairment and the risk of adverse events[ 83 ]. Based on this study, liraglutide can be used safely in patients with varying degrees of renal impairment. Liraglutide administration was well tolerated in patients with mild renal impairment since no significant differences in the rates of nausea, renal injury or minor hypoglycemia were observed compared with placebo.

No significant effect of mild renal impairment on HbA1c reduction was observed. However, a trend towards increased nausea was observed with liraglutide in the small number of patients with moderate or severe renal impairment. Overall, this meta-analysis showed that mild renal impairment determined by the Cockcroft-Gault equation did not have a significant effect on the efficacy and safety of liraglutide[ 84 ].

However, the long-term data regarding the use of liraglutide in patients with moderate-to-severe renal impairment is limited. A randomised, placebo-controlled, double-blinded trial aiming to test safety and efficacy of treatment with liraglutide in patients with T2DM and dialysis-dependent ESRD was recently announced[ 86 ]. In this trial 20 patients with T2DM and ESRD and 20 matched patients with T2DM and normal kidney function will receive liraglutide for 12 wk 9 visits in an individually titrated dose of 0.

The primary endpoint is dose-corrected plasma trough liraglutide concentration at the final trial visit aiming to determine potential accumulation in the ESRD group. Glucagon-like peptide 1; ANP: Type 2 diabetes mellitus; HbA1c: A case report described a year-old Caucasian woman who had started 1 mo earlier subcutaneous liraglutide 1. She had lost 8. Other potential causes of renal failure and adverse drug reactions due to other drugs such as ciprofloxacin and quinapril were ruled out by laboratory investigation and renal biopsy.

Renal biopsy showed that liraglutide was a likely cause of acute kidney injury through the development of acute tubular necrosis. The patient was treated with discontinuation of liraglutide, volume repletion, and hemodialysis[ 87 ]. Another case report described a year-old man with T2DM who started liraglutide aiming to a gradual reduction of insulin because of hypoglycemic episodes[ 88 ]. Three months later the patient reported that his early morning glucose levels were elevated and he had nocturia. Laboratory results revealed an increase in his creatinine concentration [from 1.

Liraglutide, ramipril, indapamide and metformin were stopped and insulin was restarted.

Effects of glucagon-like peptide-1 receptor agonists on renal function

His renal function was completely recovered a few weeks later. Similarly, a year-old man receiving liraglutide had polyuria and polydipsia. His HbA1c was Laboratory results revealed an increase in his serum creatinine [1.