Detective Nephron: Next Adventure

 Check out the July issue of 2024 Kidney News for the next Detective Nephron.

Consult Rounds: eDKA with GLP-1R Agonists

Euglycemic diabetic ketoacidosis (DKA) is a rare but serious condition characterized by ketoacidosis without significant hyperglycemia. We have seen this complication and heard about it in SGLT2i. Apparently, this can occur in patients using GLP-1 receptor agonists as well. 

GLP-1 (glucagon-like peptide-1) agonists enhance glucose-dependent insulin secretion, suppress inappropriate glucagon release, slow gastric emptying, and promote satiety. Euglycemic DKA is rare but has been reported in patients on GLP-1 agonists, particularly in combination with other diabetes medications like SGLT2 inhibitors. Why and when:- especially in type 1 diabetes (even if undiagnosed), severe illness, surgery, dehydration, and reduced insulin doses. Dehydration and changes in diet or medication regimens can also precipitate euglycemic DKA.

FAERS reporting system study confirmed this association. Using the FAERS database, The authors extracted the number of DKA reports from the first quarter (Q1) of 2004 to the fourth quarter (Q4) of 2019 and calculated proportional reporting ratios (PRRs). They then examined each FAERS file from Q1 2004 to Q4 2020 to gather detailed information on DKA reports. During the period from Q1 2004 to Q4 2019, there were 1,382 DKA cases (and 1,491 ketosis cases) linked to GLP-1RA in the FAERS database. After excluding the influence of SGLT2 inhibitors, Type 1 diabetes, and insulin, there was a slightly disproportionate reporting of DKA associated with overall GLP-1RA (PRR 1.49, 95% CI 1.24-1.79, p < 0.001). This disproportionality disappeared when GLP-1RA was combined with insulin. When GLP-1RA is not combined with insulin, there was a disproportionality of DKA reports associated with GLP-1RA. The authors's analysis of the FAERS database provides evidence and highlights the potential association between DKA adverse events and GLP-1RA therapy, which clinicians may often overlook.

Here is a case report. This case report is with GLP-1RA and SGLT2i use. Here is a summary from the UK agency. 

Diagnosis requires a high index of suspicion in diabetic patients presenting with typical DKA symptoms but normal or mildly elevated blood glucose.

Let's observe to see if we see more of these cases as more and more prescriptions are being given out in the general medicine, cards and renal community. 

Opinion: Should we focus on targeted therapy and use less of ACEi/ARB, SGLT2i?

In nephrology, we have traditionally focused on treating CKD and fibrosis, often resorting to "band-aid" therapies for many diseases. Most guidelines suggest starting with ACE inhibitors (ACEi) or angiotensin receptor blockers (ARBs), and more recently, adding SGLT2 inhibitors (SGLT2i). This approach has proven effective for diabetic nephropathy, advanced CKD, and perhaps secondary focal segmental glomerulosclerosis (FSGS). However, is this strategy appropriate for other glomerulonephritides (GNs) and disease states?

For instance, if proteinuria is high, KDIGO recommends ACEi/ARB and conservative management as the first-line treatment for IgA nephropathy (IgAN). Should we not reconsider this approach? Why not prioritize treating the underlying disease with targeted therapies first? If these fail or CKD progression continues, we could then add ACEi/ARB, SGLT2i, and other CKD medications. For example, in lupus nephritis (LN), we initially treat the disease itself. Yet, in many GNs, we start with "band-aid" medications, which often leads to the primary disease treatment being sidelined or neglected.

A paradigm shift is needed in renal medicine, especially as new targeted therapies for conditions like IgAN, C3 glomerulopathy (C3GN), membranous nephropathy, and APOL1-mediated FSGS emerge. We should consider starting with these targeted therapies, and following up with ACEi/ARB and SGLT2i as supportive measures.

I propose adopting a methodology similar to rheumatology and oncology, where disease-modifying agents are used as first-line treatments (supported by RCT data), followed by CKD agents. While there is currently no data to support this approach, a shift in mindset is necessary to design and conduct trials based on this concept. This is a lingering thought from a nephrologist who sees other fields advancing faster than ours.

Topic Discussion: Pseudo AKI with anti cancer agents

Legend: AKI, acute kidney injury, MATE, multidrug and toxic compound extrusion; OAT, organic anion transporter; OCT, organic cation transporter

As of April 2024--most updated data on anti-cancer agents and Pseudo-AKI.

Several classes of cancer treatments are associated with pseudo-AKI.  Providers must be aware of this phenomenon, as pseudo-AKI can lead to temporary stopping and even permanent discontinuation of life-saving treatments. When patients present with increases in serum creatinine while on these drugs, checking a serum cystatin C level may help differentiate true AKI from pseudo-AKI.

Shruti Gupta and Kenar Jhaveri 

Anion gap acidosis- CUTE DIMPLES

We know MUDPILES

Then came GOLDMARK

 

Now let's welcome-- CUTE DIMPLES

There are other causes of a true high anion gap metabolic acidosis that are not captured by the MUDPILES and GOLDMARK mnemonics that should be kept in mind and are included in the recently published and modified CUTE DIMPLES mnemonic presented in CJASN by Anika A et al. 

Concept Map: Hypertension in Hemodialysis

 

This is a schematic of the treatment of resistant HTN in the hemodialysis patient. Based on a review published in JASN

Figure made using biorender.com 

In the NEWS: Intravitreal Anti VEGF agents and Kidney disease

 Check out this twitter feed I had done on the topic of Intravitreal Anti VEGF agents and the Kidney.