Kidney & Heart, study & practice

Kidney & Heart, study & practice


CKD Renoprotective medicines, Non-immune drugs, MBD, Non-drug management. 



  • ACEI & ARB
  • MRA
  • Renin inhibitor 
  • Control of BP, Lipid, Glucose 
  • Bicarbonate 
  • CaCO3 additional benefit
  • Other oxalate scavengers
  • Ascorbic acid
  • Anti-oxidative stress
  • FGF 23 & CKD progression
  • Phosphate binders
  • PTH suppression
  • Mineral Bone disease
  • Medical parathyroidectomy
  • Calcimimetic cinacalcet in tertiary HPTH
  • Etelcalcetide in secondary HPTH
  • TPDI & Post TPDI protocol


  •            Dietary sodium 
  •            Glycaemic control 
  •            New agents for glycaemic control
  •            Antihypertensives
  •            Vitamin D
  •            Endothelin antagonist


  •            CKD ADVICE,
  •            Diet 
  •            Lifestyle modifications


Protect nephron
Protect nephron

Section A: CKD, renoprotective management


  2. ACEI & ARB
  3. MRA
  4. Renin inhibitor 
  5. Control of BP, Lipid, Glucose 
  6. Bicarbonate 
  7. CaCO3 additional benefit
  8. Other oxalate scavengers
  9. Ascorbic acid
  10. Anti-oxidative stress
  11. FGF 23 & CKD progression
  12. Phosphate binders
  13. PTH suppression
  14. Mineral Bone disease
  • Medical parathyroidectomy
  • Calcimimetic cinacalcet in tertiary HPTH
  • Etelcalcetide in secondary HPTH
  • TPDI
  • Post TPDI protocol



1. Angiotensin-converting-enzyme inhibitors or Angiotensin-2-receptor antagonists 

Use maximum tolerable dose. If high K is a problem, use anti high-K-medicine and continue ACEI or ARB. 


2. Mineralocorticoid receptor antagonist (MRA) 

Steroidal - Spironolactone and Eplerenone.

Non-steroidal - new agent in phase 3 trial. This can be used in low dose with ACEI or ARB. Hyperkalaemia may be a limiting factor. 


3. Aliskerin - Renin antagonist. Do not use it in CKD-3. Contraindicated because of fatal hyperkalaemia. It can be used in NON-CKD cases of hypertension with eGFR >60.


4. BP control, lipid control and DM control need to be optimized according to the guidelines.


5. Sodium bicarbonate tablets - you need to keep HCO3 level above 22. Acidosis primes renal fibrosis.


6. CaCO3 (additional benefit) - Oxalate from oxalate rich food (10% supply of urinary oxalate) reaches kidney and contributes to crystal nephropathy (oxalate nephropathy) causing progression of interstitial fibrosis with incidences of AoCKD and fast progression to ESRF. Calcium carbonate phosphate binders also bind with food oxalate and reduces it's absorption. Reduces CKD progression.


7. Other oxalate-scavengers -

Endogenous oxalate (90% suppliers of urinary oxalate) from amino acid metabolism can be reduced by pyridoxine. You can try for 3 months. Can continue if response is good.Dietary oxalate can be reduced by calcium supplements as mentioned above and with probiotic. Probiotic degrades oxalate in the gut. You can try for 3 months. Can continue if response is good.


8. Ascorbic acid - is metabolized to oxalate. This way Vitamin C and citrus fruits can fasten CKD progression. Avoid these in your patients.


9. Oxidative stress and chronic inflammation - CKD is associated with chronic inflammation, endothelial dysfunction, platelet activation and oxidative stress. CKD progression can be reduced by addressing these.

Statin - Atorvastatin has been shown to reduce endothelial dysfunction in CKD. Use it in hyperlipidemia.Allopurinol - by it's non-xanthine oxidase inhibition action. It inhibits lipid peroxidase (produces oxygen radicals), thus inhibit oxidative stress. Reduces CKD progression. If you get hyperuricemia by lab results, use it. Not much evidence to support this notion. Need further RCTs.Notes on allopurinol & HLA-B*58-01

In Chinese, Thai & Korean, Allopurinol associated drug reaction has been closely associated with HLA-B*58-01, (80-85% in positive cases while only 15_20% in negative cases). HLA-B*58-01 is common in these population than rest of Asian and European population. HLA-B*58-01 genotyping (a codominant allele) could considerably reduce the occurrence of allopurinol-induced SCARs (severe cutaneous allergic reactions) and related deaths. Cost-effectiveness analysis of treating patients with chronic gout (without additional risk factors like CKD3) in Singapore and in Portugal found that HLA-B*58:01-guided ULT (urate lowering therapy) was not cost-effective at this time.

FDA recommended gene testing in susceptible population (Chinese, Korean, Thai) only before starting allopurinol.

c.  Febuxostat

A large study of cardiovascular events in gout patients taking one of two medications to prevent excess build-up of uric acid has found that one of the drugs, febuxostat (Uloric, Takeda), increased the risk of death for those with heart disease compared with the other drug, allopurinol. Yet the two drugs were comparable with respect to a combination of nonfatal heart attack, nonfatal stroke, urgent surgery to treat angina, and death due to cardiovascular causes.

FDA advisory to use with informed consent in patients who are allergic to allopurinol.


10. FGF23 (optimization of CKD renal bone metabolism) - hyperphosphatemia from CKD is associated with upregulation of Fibroblast Growth Factor (FGF23) from renal paranchyma, also known as phosphaturic hormone. FGF23 is important in embryogenesis responsible for the fibrous tissue in the developing fetus. In CKD upregulation of it could contribute to progressive fibrosis. Control of hyperphosphatemia therefore is important in retardation of progression of CKD. Optimization of phosphate binders and vitamin D are required.


11. Phosphate binders:

a) Calcium based carbonate (Ca 40%) or acetate ( Ca 25%) with food. 

b) Noncalcium based:

  i. Lanthanum carbonate (divalent metal like calcium, binds phosphate in food. Longterm study showed deposits in bone, but impact yet uncertain).

  ii. Sevelamer hydrochloride (a resin that chelate phosphate. Also chelate lipids, drugs vitamins and other trace elements, as such needs caution for other concomitant medication use).

  iii. Magnesium hydroxide and Magnesium Carbonate, singly or in combinations of Calcium carbonate or acetate. 

   iv. Iron Magnesium Hydroxycarbonate. 

All showed good phosphate lowering affects. 


12. PTH Suppression : iPTH more than 25 pmol/l, needs suppression by: 

a) Vitamin D, if level of serum 25(OH) Cholecalciferol is less than 25.

b) Alfacalcidol / calcitriol 0.25 - 1 mcg 3 x/wk.

c) Cinacalcet (calcium mimetics) 25-50 mg daily if S Calcium is high. They mimic cakcium and bind to calcium receptor of PTH secreting clear cell of parathyroid gland. Thus inhibit the cells by negative feedback mechanism. 

d) Paracalcitriol and doxarcalciferol: these agents binds to vitamin D receptor of PTH secreting cler cells of parathyroid gland, but do not have the action on calcium absorption. 


13.  Mineral bone disease

Reference talk is in Section B no 30. 

In the end of the spectrum you get tertiary hyperparathyroidism where you need either surgical total parathyroidectomy and deltoid implant (TPDI), or incases of surgical unavailability, medical parathyroidectomy by Cinacalcet, Paracalcitriol, Doxarcalciferol. 

(Quotes from this link about Etelcalcetide): In dialysis patients who cannot take cinacalcet because of vomiting, its derivative peptide Etelcalcetide IV triweekly is used. In 2016, etelcalcetide was introduced for the treatment of secondary HPT. The peptide etelcalcetide directly agonizes the CaSR, thereby reducing circulating levels of PTH and subsequently calcium (ref). By means of a triweekly bolus injection of the drug, a sufficient plasma level of the drug is attained, enabling the administration during dialysis. This makes drug adherence easier for the ESRD patient. Etelcalcetide has been compared to both placebo as to its precursor cinacalcet (ref). 50% of the patients who received etelcalcetide showed a decrease of PTH levels to ⩽32 pmol/L. Etelcalcetide was expected to give less side effects as vomiting and diarrhea since it is administrated intravenously and thus bypasses the gastrointestinal tract. Unfortunately, no significant difference in side effects was found when comparing etelcalcetide with cinacalcet, probably due to PTH-receptors in the intestinal tract. A 30% decrease of FGF-23 levels was seen in 80% of the patients using etelcalcetide after 27 weeks. Studies investigating the long-term effects of etelcalcetide on mineral bone disease, overall survival, and cardiovascular events are not available yet. The costs of etelcalcetide are significantly higher than its precursor cinacalcet. Therefore, etelcalcetide should be used as a second in line treatment option, in patients unresponsive to oral calcimimetics or for those patients who fail to adhere properly. Etelcalcetide, like cinacalcet, is only registered for the treatment of dialysis patients, not for those who received a kidney transplant.

Daily IV Calcium gluconate infusion protocol post TPDI
Daily IV Calcium gluconate infusion protocol post TPDI

Post TPDI protocol

  • After Total Parathyroidectomy abd Deltoid Implant surgery, iPTH level plummets, so also serum calcium level (corrected for Albumin). Because of Osteoclast hyperplasia as happened due to hyperparathyroidism with resorption from bones, post parathyroidectomy the calcium starts to be taken up on bone by osteocytes, as a result calcium levels also plummet. You need to replace it Iv by cakcium gluconate (ml= mmol of ca) or Iv calcium Chloride (2-3x concentrated than gluconate).
  • The first dose post TPDI Surgery is half of serum Alkaline Phosphatase (indicative of Osteoclast activity). This is knoen as rule of thumb. The Iv cslcium needs to be givrn diluted to equal volume of NS or D5 ovrr 6 to 12 hours through CVP line.
  • Subsequent daily dose depend on daily serum calcium levels as per following protocol, until the amounts come down to 30 ml. Then only oral CaCO3 tab maximisef dise along with Active Vitamin D in maximum dose to continue. later bith medicines need to be titrated down stream.
Credible therapy, Professor Fioretto's screen
Credible therapy, Professor Fioretto's screen

Section B: CKD Non-immune drugs


  1. Dietary sodium 
  2. Diabetic medicines
  3. New agents for diabetes mellitus 
  4. Antihypertensives
  5. Vitamin D
  6. Endothelin antagonist


1. Dietary Na - reduce salt intake to 5 gm.

  • Equivalent to Action of ACEI or ARB in protecting DKD.
  • Low-sodium diet (24-h urinary sodium/creatinine ratio (mmol/g) < 121) enhanced the renoprotective and cardioprotective effect of angiotensin receptor blockers (losartan or irbesartan) in type 2 diabetic patients.


2. Glycaemic control -

  • Results from pancreatic transplant recipients in whom true euglycemia is restored suggest that strict glycemic and metabolic control may slow the progression rate of progressive renal injury even after overt dipstick-positive proteinuria has developed. 
  • This was also shown in DCCT & UKPDS studies. This is cost effective as well.


3.  New agents for DM in CKD:

a. Dipeptidyl peptidase inhibitors

  • The dipeptidyl peptidase (DPP)-4 inhibitors (ie, gliptins) in type 2 diabetes. Linagliptin, Sitagliptin and Vidagliptin. 
  • Inhibit the breakdown of the incretin hormones such as glucagon like peptide 1 (GLP-1) secreted by the GI tract in response to food intake, and leads to insulin secretion in a glucose-dependent manner, while decreasing glucagon release.

GLP-1 also slows gastric emptying.

b. Alpha-glucosidase inhibitors

  • Alpha-glucosidase inhibitors (acarbose) decrease the breakdown of oligosaccharides and disaccharides into monosaccharides in the small intestine, slowing the absorption of glucose.
  • Adverse effects are bloating, flatulence, and abdominal cramping. Minimally absorbed, with less than 2%.

c. Sodium-glucose cotransporter 2 (SGLT2) inhibitors.

  • Inhibits renal glucose absorption in the proximal tubule, the site in the kidney where approximately 90% of glucose reabsorption occurs.
  • This leads to increased excretion of glucose in the urine. Also accompanied by increased urinary excretion of sodium, which helps further blood pressure lowering.
  • This explains additional cardiovascular and renal benefits.
  • If patient is on insulin, to continue, otherwise there is increased incidence of amputation.
  • Even though, it is indicated in patients with eGFR of more than 30ml/min, many nephro-cardiologist across the world use it in moderate CKD with eGFR as low as 16ml/min.

d. Glucagonlike peptide-1 (GLP-1) receptor agonists or incretin mimetics

  • The GLP-1 agonists exenatide and liraglutide are also known as injectable incretin mimetics.
  • These drugs promote insulin release, delay glucagon release, and slow gastric emptying and are less likely to cause hypoglycemia.
  • They may cause pancreatitis and acute renal failure.

e. Amylin analogs

Amylin is a peptide co-secreted with insulin and is deficient in diabetes. Its actions are complementary to insulin in regulating plasma glucose. Amylin reduces postprandial glucagon.

Pramlintide - Amilin analog is given as an injection with insulin. Dose adjustment for pramlintide are not required in the presence of mild-to-moderate renal failure.


4. Antihypertensives in DKD

Careful blood pressure control is needed to prevent the progression of diabetic nephropathy and other complications; however the optimal lower limit for systolic blood pressure is unclear. In the UKPDS, a 12% risk reduction in diabetic complications was found with each 10 mm Hg drop in systolic pressure, the lowest risk being associated with a systolic pressure below 120 mm Hg. SPRINT study showed similar result in all, but at the expense of increased incidence of hypotension and mortality.


ACE inhibition has been shown to delay the development of diabetic nephropathy. In the ACE inhibition arm of a large trial, only 7% of patients with microalbuminuria experienced progression to overt nephropathy; however, in the placebo-treated group, 21% of patients experienced progression to overt nephropathy. The beneficial effect of ACE inhibition on preventing progression from microalbuminuria to overt diabetic nephropathy is long-lasting (8 years).

b. ARB

Both DM1 & DM2 are characterized by the appearance of microalbuminuria, which leads to overt proteinuria and progressive loss of GFR. A series of renal biopsy samples from patients with type 2 DM and proteinuria revealed that a significant proportion of these patients had glomerular lesions other than the classic lesions associated with type 1 diabetic nephropathy.

Two studies (the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan [RENAAL] Study and the Irbesartan Diabetic Nephropathy Trial [IDNT]) demonstrated that angiotensin II receptor blockers (ARBs) are superior to conventional therapy and amlodipine in slowing the progression of overt nephropathy.

c. Both ACEI & ARB.

All of you agree that the combination is not good. ON-TARGET and NEPHRON-D studies showed that.

d. ALISKIREN... contraindicated in eGFR <60 ml/min.


5. Vitamin D

May have a role in renin inhibition, and vitamin D supplementation may be useful in reducing proteinuria in patients with diabetic nephropathy. Patients with diabetic nephropathy with stage 3 chronic kidney disease (eGFR 59 – 30 mL/min/1.73 m2) or more advanced stages should be evaluated for their vitamin D and parathyroid hormone status as recommended (KDIGO).


6. Endothelin Antagonist 

   AvosentanEndothelin antagonists have demonstrated antifibrotic, anti-inflammatory, and antiproteinuric effects in experimental studies. It reduces proteinuria and BP when added to ACEI or ARB.


Morbidity & mortality
Morbidity & mortality



    2. Diet and
    3. Lifestyle modifications


    The pills cannot heal unless you go extra miles with patient education for life long diseases. Go to the following link, and let your patient toggle it anywhere anytime lifelong. 

    1. Renal failure advice

    2. Food- the other important thing that goes through mouth othe then drugs, is food. Must be careful. Common items may have problem with kidney issues.

    3.  Lifestyle care - kidney is vulnerable to many other factors pertaining to lifestyle. Patient needs to be aware of it.