Hyponatremia, a condition characterized by low sodium levels in the blood, is often precipitated by excessive water intake which dilutes the body’s sodium concentration. In the elderly, the kidneys’ ability to excrete free water is often compromised due to age-related decline in kidney function and the use of medications such as diuretics. Thus, when nephrologists advise increased fluid intake , they may inadvertently exacerbate or induce hyponatremia.

I remember those dedicated enthusiastic patients who, in their determination to avoid dialysis, would consume over 4 liters of water per day. They come and explain to you how strict they are with calculating their water intake amount, how they make reminders on their phones, and how they keep a glass of water beside them on every occasion. They may even enter the clinic with their bottle of water and drink it in front of you to prove it. Some of them, when they hear about acidosis, thought of carbonated water as a source of water and bicarbonate, and shifted all their water into carbonated water aiming for better results. Unfortunately, they may present with symptoms of lethargy and confusion due to nephrologist induced hyponatremia.

Furthermore, many CKD patients are also advised to adhere to a low-salt and low-protein diet, which can complicate the condition more and more. The reduction in sodium intake coupled with excessive water consumption can further dilute the sodium level in their bloodstream, exacerbating the condition. It’s crucial for us, as healthcare providers, to regularly monitor the effects of our dietary recommendations and adjust them based on individual patient responses.

Although the ISN World Kidney Day in 2015 promoted increased water consumption with suggestions that it “might protect the kidneys,” substantial evidence on the impact of hydration on slowing CKD progression remains scarce. Recent studies (CKD-WIT, and CKD-REIN) evaluating the efficacy of increased water intake for delaying CKD progression have not shown significant benefits.

As nephrologists, we bear the responsibility to ensuring our advice does not inadvertently harm those we aim to help. We must recognize the potential risks associated with our therapeutic recommendations and strive for a balance that preserves patient safety and quality of life.

Regards,
Mohamed

FSGS Over IgAN: Regional Studies Show a Shift

In Egypt, a review of glomerular diseases found IgAN significantly less common than FSGS among patients who underwent kidney biopsies (Elrggal and Zyada, 2024).

Similarly, a systematic review across Africa reported an overall pooled prevalence of FSGS at 26.1%, and surprisingly IgAN 2.6%​ (Ekrikpo et al, 2023).

In Saudi Arabia, FSGS was the most common primary GN as well, constituting 35% of the primary renal pathologies observed in a study from the Eastern region (Alkhunaizi, 2007). IgAN, while still present as the second most common primary GN, was significantly less prevalent at 14%​.

Several factors may contribute to the higher prevalence of FSGS over IgAN in these regions:

1. Genetic Factors:
   • Genetic Variants: Particularly in Africa, the APOL1 gene variants are associated with a higher risk of developing FSGS. These variants are prevalent among African, likely contributing to the higher rates of FSGS​.
2. Environmental and Socioeconomic Factors:
   • The variance in environmental and socioeconomic factors across these regions, including access to healthcare, could influence which conditions are more likely to be diagnosed or treated.
3. Underreporting and Diagnostic Practices:
   • In many parts of Africa, there is limited access to comprehensive diagnostic facilities, which might underreport cases of IgAN due to the lack of immunofluorescence and electron microscopy necessary for its diagnosis.

Conclusion: A Call for Updated Regional Nephrology Curriculums

These findings underscore the importance of regional studies in understanding the epidemiology of glomerular diseases traditionally taught from a Western-centric viewpoint. Future studies should aim to elucidate the reasons behind these regional differences, with a focus on genetic research and improvements in diagnostic practices.

Regards,
Mohamed

We recently encountered a situation with a patient who inserted a permanent hemodialysis catheter in another center, and it was not functioning at all. The AP Chest X-ray revealed a kink in the top notch of the catheter as seen in the following image:

Our intervention nephrologist, Dr. Hassan Foula ordered a lateral X-ray, and surprisingly it revealed this:

The patient was prepared for OR intervention, under C-arm guidance, the first catheter was removed, a new catheter was inserted, and confirmed its location using C-arm and this was the follow up X-ray using both AP and lateral view:

Conclusion:
Lateral X-ray can reveal significant findings that are hidden from the AP view.
We are starting to use more and more lateral X-ray views to ensure the appropriate position of our HD catheters, to avoid malposition and consequently malfunction.

Share your experience! Do you support the use of lateral X-rays after placing HD catheters?

Sacubitril/Valsartan has been used successfully to treat heart failure with reduced ejection fraction (HFrEF). However, patients with end-stage kidney disease (ESKD) on maintenance dialysis are consistently excluded from major clinical trials. Recently, a systematic review addressing the Cardiovascular Benefits and Safety of Sacubitril-Valsartan in ESKD has been published in KI reports by Mariam Charkviani and colleagues. 

The analysis involved 12 observational studies with 799 eligible ESKD patients. The results showed that LVEF significantly improved in patients with HFrEF (EF <40%) and HFmrEF (EF 40-50%) with mean difference of 12.42% (95% CI: 9.39, 15.45). However, patients with HFpEF (LVEF >50%) did not exhibit statistically significant effect.

Safety analysis indicated no differences in incidence of hyperkalemia (pooled odds ratio [OR] 0.72; 95% CI: 0.38, 1.36) or hypotension (pooled risk ratio [RR] 1.03; 95% CI: 0.36, 2.98). No cases of angioedema were reported.

Are there any ongoing or published trials using Entresto in dialysis patients?

A PubMed search with the terms (sacubitril valsartan AND heart failure AND dialysis) with a clinical trial filter, revealed only a single recently published trial of Sacubitril/Valsartan in dialysis patients with HFpEF.

A clinicaltrials.gov search with the same terms revealed 2 trials from China, but no results were reported.

The nephrology community deserve a clinical trial about the efficacy and safety of Sacubitril/valsartan in ESKD patients on maintenance dialysis.

A challenge appears after the improvement of heart failure condition, whether or not to create an AVF if the patient was dependent on a permanent catheter for hemodialysis, share your thoughts!

The primary end point was mortality due to cardiovascular disease (CVD).
Secondary outcomes included all-cause mortality, combined fatal and nonfatal (morbidity) CVD, and both mortality and morbidity for coronary heart disease, stroke, heart failure, end-stage renal disease, and cancer.

Results:
Primary outcome: Cardiovascular disease mortality rates per 100 persons were similar between the 3 groups 23.7, 21.6, and 23.8 in the diuretic, CCB, and ACE inhibitor groups, respectively, at 23 years after randomization (aHR, 0.97 [95% CI, 0.89-1.05] for CCB vs diuretic; aHR, 1.06 [95% CI, 0.97-1.15] for ACE inhibitor vs diuretic).
Secondary outcomes: The long-term risks of most secondary outcomes were similar among the 3 groups. Compared with the diuretic group, the ACE inhibitor group had a 19% increased risk of stroke mortality (aHR, 1.19 [95% CI, 1.03-1.37]) and an 11% increased risk of combined fatal and nonfatal hospitalized stroke (aHR, 1.11 [95% CI, 1.03-1.20]).

These results confirm the results of a previous 8-13 years follow up study of ALLHAT participants, which found that during the posttrial period, no significant differences were detected among the 3 treatment groups for the primary outcome. Compared with chlorthalidone, the risk of HF was higher for the amlodipine group, and the risk of stroke mortality was higher for the lisinopril group (particularly for Black participants).

It was also found that Lisinopril had a 19% increase in risk for kidney disease mortality compared with chlorthalidone over the 23 years of follow-up (HR, 1.19 [95% CI, 1.00-1.41]; Table 2), but this was not statistically significant after covariate adjustment (aHR, 1.18 [95% CI, 0.97-1.44]; Table 3)

Another trial was published also in December 2 years back:

In December, 30th, 2021, NEJM published a RCT for the use of Chlorthalidone in advanced CKD. The primary outcome was the change in 24-hour ambulatory systolic blood pressure from baseline to 12 weeks. Secondary outcomes were the change from baseline to 12 weeks in the urinary albumin-to-creatinine ratio, N-terminal pro–B-type natriuretic peptide level, plasma renin and aldosterone levels, and total body volume. Safety was also assessed.

The study found that among patients with advanced CKD and poorly controlled hypertension, chlorthalidone therapy improved blood-pressure control at 12 weeks as compared with placebo. However, Hypokalemia, reversible increases in serum creatinine level, hyperglycemia, dizziness, and hyperuricemia occurred more frequently in the chlorthalidone group than in the placebo group.

Unfortunately, Chlorthalidone, or any other thiazide diuretics are not present as sole drugs in Egypt, and are only present as combinations wither with RAAS blockers or with beta blockers. I don’t know the cause behind this? But it should be made available, because we are already lacking many other anti-hypertensive agents in the market, like Hydralazine for example.

Regards,
Mohamed Elrggal, MD

Either spontaneously or post treatment.

Risk factors: Older age, CKD, high tumor burden, use of nephrotoxic drugs

Clinical: AKI, convulsions, arrythmia, sudden cardiac death (-3: +7 days of treatment)

Labs: Urea, creatinine, uric acid, K, Calcium, phosphorus, LDH

Definition: 2 or more electrolytes disturbance

Prevention:
Hydration with IV fluids, aim 100 ml/hour, monitor for volume overload.
Urinary alkalinization is no longer recommended and is potentially harmful. Concomitant hydration and depletion (forced diuresis) can be hazardous, and association with cytokine-mediated hemodynamic instability.
Hypouricemic agents (Allopurinol (for mild and moderate risk), febuxostat (for severe risk)) to be started 48–72 hours before chemotherapy.

Treatment:
Anuric AKI: Careful volume assessment and IV fluids administration (decrease to avoid overload).
Asymptomatic hypocalcemia should not elicit calcium supplementation that may increase the risk of calcium–phosphate precipitation.
HD: indications for KRT include threatening hyperkalemia, prolonged oligo-anuria, and fluid overload. Intermittent hemodialysis allows for the administration of chemotherapy in the interval between two sessions. CKRT allows for removal of the ongoing released intracellular contents. PIRRT combines the benefits of both regimens.

Source: How I Treat Tumor Lysis Syndrome article @cJASN

Regards,

Mohamed Elrggal, MD

At AlQabbary nephrology department, we had to insert a permanent external iliac HD catheter, for a patient with multiple access failure. We didn’t have fluoroscopy at that day.

Under US guidance, the external iliac vein was localized and punctured. The guide wire was inserted and the subcutaneous track was made, then the catheter was inserted successfully.

To ensure the placement of the catheter, POCUS examination of the epigastric area revealed this nice view of the catheter tip inside the IVC. The catheter was functioning very well on the HD machine immediately after insertion.

US can help non-fluoroscopic insertion of permanent HD catheters. Read also this clinical research recently published in KI-reports about “Feasibility Analysis of Ultrasound-Guided Placement of Tunneled Hemodialysis Catheters” and the accompanying editorial discussing “non-fluoroscopic techniques to insert a tunneled hemodialysis catheter”.

I recently got a 68-years-old female with systemic sclerosis and SRC who is maintained and stable on Ramipril, steroids 5 mg, hydroxychloroquine with an ESR of 20 in the first hour. She also has T2DM, maintained and controlled on Metformin and insulin glargine, and controlled hypertension using Ramipril.

She presented with dry cough, which doesn’t have any evident cause, apart from being ACEi-induced! Her rheumatologists asked her to visit her nephrologist to take his advice.

Multiple questions has emerged during my talk with the patients:

1. Can ARBs replace ACEi in patients with stable SRC?
2. Is there any possible alternative diagnosis, that could cause her chronic cough?
3. Is there any benefit of adding additional treatment to control and preserve her kidney condition?

For the first question, a quick UpToDate search found this:

For patients who are unable to take an ACE inhibitor (eg, due to allergy), an ARB is an alternative option. However, it is not known whether ARBs are as effective as ACE inhibitors, since these agents have not been adequately evaluated in the treatment of SRC.

I took advantage of her stable SS status, minimal dose of prednisolone (5mg), minimal proteinuria and normal GFR to shift from Ramipril to Valsartan and will monitor the response within 3 months.

For the second question regarding other differential diagnoses:

While revising her immune markers, I found that her Microblot array revealed positive ANA, Anti Scl70, and anti Ro 52. A quick pubmed search found that Anti Ro52 is associated with lung fibrosis and interstitial lung disease in SS, dermatomyositis and other mixed connective tissue diseases. Could her chronic cough be due to ILD which developed while she was on steroids. She has been on steroids for a year now!

For the third question:

I considered adding a SGLT2i (Dapagliflozin 10mg), which will help reducing her proteinuria, halting CKD progression and control her diabetes. The safety of SGLT2i in immunosuppressive patients has been shown in multiple cohorts.

Additionally, as Endothelin is incriminated in the pathogenesis of SRC due to its vasoconstrictive effects, it seems logic to use Endothelin receptor antagonist (ERA) like Bosentan for management of SRC. While the results were not significantly different from ACEi treatment, ERA use was feasible, associated with decreased serum creatinine, but caused some peripheral oedema and elevated aminotransferases.
I actually didn’t add Bosentan to her medical prescription, as her condition is very much stable without the need for additional treatment.

Will keep you updated about the progress of her interesting case.

Regards,
Mohamed

Her recently inserted permanent IJ HD catheter was not functioning well, despite an appropriate placement under C-arm guidance. A POCUS assessment of her volume status revealed this:

A collapsed IVC which perform a flap valve effect on the catheter, leading to catheter malfunction during blood withdrawal. The patient took 1.5 L of isotonic saline and the catheter started to be functioning again. A decision was made to estimate the UF each session based on POCUS assessment of the volume assessment.

We previously reported the safety of KD in an obese CKD patient. The patient had a stable eGFR during his KD regimen together with successful weight loss as shown in the following chart:

In the RESET-PKD pilot trial on short-term ketogenic interventions in ADPKD patients, KD was feasible for ADPKD patients in daily life. KD caused significant change in total liver volume, without significant change in total kidney volume. This study may indicate the need for longer duration of the intervention.

KD remains on board for ADPKD patients till ongoing clinical trial results appear. KD has many potentials as a therapeutic option for ADPKD, as it suggested to enhance metabolic reprogramming. ADPKD patients in Egypt are deficient in treatment options due it the unavailability of Tolvaptan! Patients are desperate to find alternative solutions to this progressive incurable disease.