JOURNAL CLUB: Metabolic Acidosis and improving GFR

We discussed a fascinating article from KI at Journal Club this week. It sheds some light on metabolic acidosis in CKD patients.  As we all know metabolic acidosis can cause symptoms and in some studies worsens the progression of CKD.  It also leads to Malnutrition Inflammation syndrome. 
Few papers early in the 1990s showed that if you keep the ph >7.4, there might be hastening of the renal injury. It never cought on the renal community probably for two reasons: NaHCo3- people thought might worsen the HTN of the patient. Na citrate might not be a good combination with then used aluminium binders.
This study ( although small ) with 30-40 patients ( only HTN nephropathy) showed that the rate of GFR decline was slower in the Na citrate treated group after 30 months of treatment.  What showed statistical significance was eGFRcys and Pcys and eGFRcrt and Plasma Crt were almost reaching significance but didn't.  At 6 months, there was no difference. SBP was not different at 6 months and 30 months in both groups. The bicarbonate differnce was 19 vs 23.  They hence suggest keeping bicarbonate >22 with help of Na citrate.
Few points.
1. NaHC03 can also be used. The NACL is what really causes worsening HTN for two reasons, one because of the ECF distribitution of NAHC03 is not as great as NACL. Second, the macula densa really senses Cl and not Na and if you think about it, HTN is more of a CL related problem and not Na.
2. This article touches on a pathophysiology of endothelin. When there is renal injury endothelin in the kidney is produced that can cause more damage. So in summary, CKD can lead to Metabolic acidosis.
Metabolic acidosis on one hand can cause increase kidney H+ and that causes increase endothelin which via ETA receptors leads to IF/TA and via ETB receptors to proximal and distal H secretion to mitigate the metabolic acidosis. On the other hand, this metabolic acidosis leads to increased ammonium production that leds to complement activation and IF/TA and worsening of the CKD. 
3. So aggresively treating the Metabolic acidosis with simple and cheap medications like Nacitrate or Na HCO3 might be helpful.
4. Small study, need larger studies to confirm this as it might not be significant when we bring in Diabetics, other GNs and other CKD patients. at this point, KDOQI does recommend to keep Bicarb around 22 in CKD 3,4,5 and ESRD patients.

A few more references:
http://www.ncbi.nlm.nih.gov/pubmed/2993363
http://www.ncbi.nlm.nih.gov/pubmed/19608703