In children with type 1 diabetes (T1D) who presented with diabetic ketoacidosis, the presence of acute kidney injury during the episode was associated, 8 years later, with a fivefold increased risk for diabetic kidney disease.

This finding, from an Argentine study published in the journal AndesPediátrica, underscored the importance of diagnosing T1D before ketoacidosis occurs and the recommendation to assess kidney function during the episode and in subsequent follow-up of patients.

“The rationale for publishing the study stems from the high prevalence of ketoacidosis at the onset of T1D. It is frequently associated with acute kidney injury, which often goes unnoticed immediately because it is considered part of dehydration and resolves within the first few hours of treatment. However, it can leave underlying kidney damage that predisposes patients to diabetic kidney disease in the near future,” Carla Mannucci, MD, a pediatrician specializing in nutrition, a master’s degree holder in diabetes, a member of the staff at the Hospital General de Niños Pedro de Elizalde, Buenos Aires, Argentina, and one of the authors of the publication, told Medscape’s Spanish edition.

The retrospective, preliminary case-control study included data from 59 patients with T1D and a history of ketoacidosis at onset who had been treated at the aforementioned medical center; at the time of diagnosis, they had a median age of 5 years, and 47.5% were women. None of the participants had comorbidities unrelated to the endocrinological condition, nor did they have a history of impaired renal function or abnormal ultrasound findings prior to the acute event.

The cases (n = 17) were characterized in the clinical records by T1D with diabetic ketoacidosis at onset and diabetic kidney disease 8 years after the episode, whereas the control individuals (n = 42) had similar clinical characteristics, with the exception of the presence of chronic kidney disease during follow-up.

Acute kidney injury was diagnosed and staged using the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Diabetic kidney disease was identified by the presence of albuminuria, defined as 30-299 mg/24 hours or a urine albumin-to-creatinine ratio of at least 30 mg/g in two of three repeated morning urine samples collected over 3-6 months, or by overt proteinuria, defined as at least 300 mg/24 hours or a protein-to-creatinine ratio > 0.2 mg/g in morning urine. An estimated glomerular filtration rate < 90 mL/min/1.73 m², calculated using the Schwartz formula, also supported the diagnosis.

Diabetic ketoacidosis in this patient group was treated in accordance with clinical guidelines from the International Society for Pediatric and Adolescent Diabetes. During follow-up, patients were seen every 3 months, with each visit including a physical exam, blood pressure checks, and glycated hemoglobin assessment. Annual testing also included renal, thyroid, and lipid panels, as well as anti-transglutaminase antibody testing. In addition, patients underwent yearly ophthalmologic, cardiac, and neurologic evaluations.

Acute kidney injury occurred in 22 of the included patients, representing 37.2% of the cohort, and was identified at the time of admission. Most cases were grade 1, defined as a creatinine rise of at least 0.3 mg/dL within 48 hours or 1.5-1.9 times baseline, and most patients presented with polyuria. During follow-up, three patients experienced recurrent acute kidney injury, all of which were grade 1 and associated with diabetic ketoacidosis.

No patient with acute kidney injury required dialysis, and renal function recovered with treatment of the underlying condition. Furthermore, among those with diabetic kidney disease, no decline in estimated glomerular filtration rate was observed during follow-up; however, pathologic albuminuria was observed in 15 patients and pathologic proteinuria in two.

Compared with control individuals, cases had higher glycated hemoglobin levels from disease onset, along with a greater frequency and severity of acute kidney injury, including more grade 2 and grade 3 events. Notably, acute kidney injury was present at presentation in 70.5% of patients in diabetic kidney disease group vs 23.8% of those in the control group.

Finally, following a multivariate analysis, only a history of acute kidney injury remained associated with diabetic kidney disease at 8 years of follow-up (odds ratio [OR], 5.4; 95% CI, 1.18 to 24.6; P = .02).

Mannucci noted that the study’s findings highlighted the impact of acute kidney injury on this group of patients with diabetic ketoacidosis — a complication that, as noted, often goes unnoticed in clinical practice.

“This is the first study conducted on children in Argentina, and it emphasizes the need for measures to prevent diabetic ketoacidosis at onset — not only because of the severity and risk of mortality associated with this acute complication but also because this history can accelerate the degenerative process in the kidneys, increasing the risk of chronic complications,” the specialist stressed.

Florencia Grabois, MD, a pediatrician specializing in child nutrition, a staff member at Bouquet Roldán Hospital and the EDIANE Center, a professor at the National University of Comahue, and coordinator of the Pediatrics Committee of the Argentine Diabetes Society in Neuquén, Argentina, said she considered the research “highly relevant.”

“The finding that the presence of acute kidney injury during the onset of diabetic ketoacidosis increases the risk of developing diabetic kidney disease more than fivefold in subsequent years is an invaluable contribution to pediatric diabetology,” stated Grabois.

She added that the study’s strength lies in the fact that it comes from a leading center with extensive experience in pediatric diabetes and provides regional data that is particularly relevant for Latin America.

Furthermore, in line with the article’s authors, the specialist noted that it will be important to confirm these preliminary findings through multicenter, prospective studies involving a larger number of patients.

Increasing Vigilance Regarding Acute Kidney Injury

For clinical practice, the study highlighted the need to pay closer attention, during an episode of diabetic ketoacidosis, to the potential impact on kidney function due to acute kidney injury. Mannucci added that this complication is often not assessed during acute episodes of diabetic ketoacidosis, and even when it is, there is no distinct treatment protocol.

The specialist clarified that in many cases, acute kidney injury resolves within the first few hours of treatment for diabetic ketoacidosis through rehydration and normalization of the internal environment; however, this kidney injury can leave tubular damage that subsequently compromises long-term kidney function.

Furthermore, since children are not typically categorized as being at higher risk of developing diabetic kidney disease, renal involvement may not be screened for in subsequent years, leaving the door open to irreversible damage.

Grabois agreed that during diabetic ketoacidosis, care tends to focus on critical and immediate issues, such as hydration, correction of acidosis and internal environment, treatment with insulin, and prevention of neurological complications.

“In that context, acute kidney injury may take a back seat or be interpreted simply as a transient disturbance associated with dehydration. However, current evidence shows that this is not always a harmless phenomenon and that it can have significant prognostic implications,” she added.

Furthermore, she noted that identifying acute kidney injury in this setting can be challenging because patients often present with osmotic polyuria, and baseline creatinine levels are not always available.

“This requires treatment teams to maintain a high index of suspicion and to conduct a systematic assessment of renal function throughout the entire episode,” she emphasized.

The Key Lies in Preventing Episodes of Diabetic Ketoacidosis

Both interviewees noted that the research reinforced how valuable it is for the pediatric population to receive a diagnosis of T1D before presenting with diabetic ketoacidosis.

Grabois added that the incidence of diabetic ketoacidosis at the time of T1D diagnosis can range from 13% to 80% globally. In Argentina, the figure is around 40%, and of these reported cases, more than 60% are severe, representing a significant public health challenge.

“The best strategy to prevent acute kidney injury associated with diabetic ketoacidosis is to prevent diabetic ketoacidosis from occurring in the first place. The International Society for Pediatric and Adolescent Diabetes guidelines emphasize that diabetic ketoacidosis remains one of the leading causes of morbidity and mortality in children and adolescents with T1D,” said Grabois.

She added that “prevention of diabetic ketoacidosis begins before diagnosis through awareness campaigns targeting the community, families, healthcare teams, and teachers, to promote early recognition of diabetes symptoms.”

She also agreed with Mannucci on the growing importance of detecting various autoantibodies against pancreatic beta cells in achieving an early, presymptomatic diagnosis in children with T1D.

“For several years now, studies have been conducted in Europe and the US to screen for T1D through autoantibody testing. This year, this initiative will begin in our country at some pediatric centers, including Elizalde Hospital, where I work,” Mannucci announced.

This research will allow patients at certain stages to even access treatments to prevent the clinical progression of T1D; or, in cases where this is not feasible, it will help ensure they receive multidisciplinary care at an earlier stage.

Grabois emphasized that once a diagnosis has been made, diabetes education is a fundamental tool for preventing recurrent episodes of diabetic ketoacidosis and the onset of other diabetes-related complications.

She noted that, in this regard, specialized teams generally work continuously with children, adolescents, and their families during clinic visits, but they also offer educational strategies that extend into schools and sports settings through educational programs.

This is the case with the SENDAS KIDS program, an initiative that has been successfully implemented nationwide for several years, whose goal is to help children and adolescents with T1D develop self-management skills, early recognition of decompensations, proper blood glucose monitoring, management of sick days, and prevention of episodes of diabetic ketoacidosis in the school setting.

Finally, the results of the Argentine study not only raised concerns for the specialist but also reinforced the need for early intervention in T1D.

“On the one hand, they confirm that a complication occurring in the first few hours after diagnosis can leave a biological mark with a potential impact on the patient’s future course. On the other hand, they show that there is a concrete opportunity for prevention,” concluded Grabois.

Mannucci and Grabois disclosed having no relevant financial relationships.

This story was translated from Medscape’s Spanish edition.